Osteoporosis Flashcards by Jbun L

Osteoclast vs osteoblast

Osteoclast (resorption of bone)
Osteoblast (rebuilding of bone)

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When does osteoporosis occur?

When there is an imbalance in the osteoclast and osteoblast function
- bone formation does not replace resorption

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What is a major contributor to an increased risk of osteoporosis in older female patients?

Menopause

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What BMD T-score defines osteoporosis?

BMD T-score ≤−2.5

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What does this score indicate?

2.5 standard deviations below a normal young adult reference

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What conditions are associated with increased risk of fractures if patient is postmenopausal or 50-64 years of age?

Postmenopausal or 50-64 years of age with:
- Parent with hip fracture
- Osteopenia on x-ray
- Current smoking
- High alcohol intake
- Low body weight <60kg
- Major weight loss

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What conditions are risk factors for fractures regardless of age?

History of fragility
Premature menopause (<45)
Hyperthyroidism
Cushing syndrome
Hyperparathyroidism
Renal diseases
Organ transplantation
GI diseases (gastric surgery, bariatric surgery)
Disorders associated with rapid bone loss or fracture (Ex: RA, multiple myeloma)

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What medications are associated with increased risk of fractures?

Androgen deprivation therapy
Anticoagulants
Antiepileptic drugs
Antiretroviral therapy
Aromatase inhibitors
Chemotherapy
Corticosteroids (prolonged)
Cyclosporine
Loop diuretics
PPI
SSRII
Thiazolidinediones
High dose Vitamin A
Sedatives/antipsychotics that increase the risk of falls

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What tool is good for identifying fracture risk?

Fracture risk assessment tool (FRAX)

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What tool is good for identifying bone density?

CAROC system

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How can therapeutic choices for osteoporosis be divided into?

Prevention and treatment

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Which population is prevention therapy particularly important for?

Patients on chronic corticosteroid therapy

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What are non-pharm choices that we should recommend for everyone?

Regular exercise
- weight bearing, strength training

Fall prevention
- minimize physical hazards and drugs

Dietary supplement
- protein, calcium, vitamin D

Avoid excessive alcohol and caffeine

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How should the nutritional supplement of calcium be managed?

Diet first, and then supplement if necessary

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Is calcium supplementation associated with increased risk of CV events?

No. Recent data has refuted this claim.

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Vitamin D deficiency is a major issue in Canada. Requirements are often not met in diet. How much Vitamin D is recommended by Osteoporosis Canada?

800-2000 units of Vitamin D/day for those over the age of 50 and are at risk of osteoporosis.

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Is there any benefit/harm with going above this amount?

No benefit.
Seems to have enhanced bone loss when Vit D doses exceed 4000 units per day.

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What agents are used to treat osteoporosis?

Antiremodelling or antiresorptive agents

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Why is antiremodelling a more accurate description compared to antiresorptive agents?

They do more than suppress osteoclast activity. They also reduce resorption and bone formation.

Corrects remodelling imbalance

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Which drug class in the mainstay of osteoporosis treatment?

Bisphosphonate

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Which drugs are under the bisphosphonate drug class?

Alendronate
Risedronate
IV zoledronate

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Bonus: What must be corrected prior to initiating therapies like Prolia or Jubbonti?

Hypocalcemia

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What is the mechanism of action for bisphosphonates?

Bind to bone mineral
When osteoclasts being bone-resorption, they secrete acid to dissolve bone mineral
Acidic environment allows bisphosphonate to cross cell membrane and enter osteoclast -> cause apoptosis

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Of the bisphosphonates, which two agents are considered first-line?

Alendronate and risedronate

Etiodronate was the first bisphosphonate to be used but is used less commonly now

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Is there a difference in endpoints between alendronate and risedronate?

Alendronate had greater effect on BMD, but fracture prevention showed no difference. Another study showed that risedronate had greater fracture prevention than alendronate

What administration counselling points must be discussed with patients?

Take on an empty stomach Water only

What are main side effects with bisphosphonates?

Minor GI upset Allergic reactions

When is IV zoledronate used?

Can be a first-line agent if: Patient cannot tolerate GI side effects of oral agent When oral agents are ineffective Unable to adhere to admin instructions Adherence (IV is only once a year)

Is there evidence that bisphosphonates interfere with the process of fracture healing?

What type of fractures have there been case reports of with the use of bisphosphonates?

Atypical femoral fractures Similar to stress fractures but are spontaneous

Patients treated for ≥___ years with bisphosphonate had a chance of developing atypical femoral fractures.

In contrast, the incidence of "typical" hip fracture is also high. However, after ___ years of bisphosphonate therapy, the risk of AFF associated with bisphosphonate therapy appears to far outweigh the number of hip and clinical fractures prevented

With this knowledge in mind, how should we manage atypical femur fracture?

Encourage patients who are not at high risk of osteoporotic fractures to stop bisphosphonates after 5 years of therapy. If continuing for >5 years, advise patient to monitor. - Thigh or groin pain that may be unilateral or bilateral.

Following the cessation of bisphosphonate, how long does it take for risk of AFF to decline?

Within a year

If AFF is identified, how do we manage?

Do not restart bisphosphonate. Consider an anabolic agent like teriparatide to increase bone turnover and hasten repair Refer patient to osteoporosis specialist. Consider alternative therapy like estrogen, denosumab etc.

When are bisphosphonate drug holidays usually recommended?

If patient has stable BMD and has been free of fractures during therapy: After 5 years of oral therapy or 3 annual infusions of IV zoledronate

How long are drug holidays usually?

1-3 years

What biologic drug class is approved for the treatment of osteoporosis?

RANK Ligand Inhibitors

What drugs are considered RANK ligand inhibitor?

Denosumab Jubbonti (biosimilar)

What is the mechanism of action of RANK ligand inhibitors?

Prevents interaction with RANK receptors on the surface of osteoclasts. Regulates RANKL pathways Suppresses bone resorption and increases BMD

Denosumab should be considered as first line. However, ______ is what limits its use compared to bisphosphonate.

Price

Practitioners often use denosumab first line in those with _______ cases of osteoporosis. These include?

Severe - history of osteoporotic fracture - multiple risk factors for fractures - those who have failed or are intolerant of other therapies

Are drug holidays recommended for denosumab? Why?

No. Unlike bisphosphonates, denosumab is not retained in the skeleton. If therapy is stopped for more than 6 months, there is rapid increase in bone remodelling. Generally well tolerated. Infrequent cases of AFF and ONJ

What is a side effect we must monitor for with denosumab?

Hypocalcemia Particularly in patients with Vitamin D deficiency renal insufficiency

Are bisphosphonates safe in renal insufficiency?

Is denosumab safe in renal insufficiency?

Yes

What are alternatives to bisphosphonates?

Estrogen Raloxifene Teriparatide Denosumab Calcitonin

What drug is under the SERM (selective estrogen receptor modulator) drug class?

Raloxifene

What is the mechanism of action of raloxifene?

Estrogen antagonist in breast and uterine tissue, but has estrogen like activity in bone and lipid metabolism

What increased risk does raloxifene come with?

Like estrogen, it may increase risk of deep vein thrombosis and pulmonary embolism in postmenopausal women

When does raloxifene come into play?

In postmenopausal bone loss as second line therapy

What is E/PT therapy?

Estrogen Estrogen/progesterone hormone therapy

When does E/PT therapy come into play?

For those experiencing early menopause (before 45 y). Should be taken until age of menopause (~51 years of age)

E/PT therapy used to be considered first line in post-menopausal women. However, it is no longer recommended. What population may this still be true in?

May still be used first-line in post menopausal women if patient would like a prevention therapy and who also wish to receive treatment for menopausal symptoms (Ex: vasomotor symptoms)

If they do choose to use this therapy, what risks should the patient be educated on?

Reduction in hip and other fractures must be balanced against the increased risk of breast cancer and heart disease

Salmon calcitonin nasal spray used to be recommended as second line therapy. However, why was it discontinued?

Increased risks of cancer

As an alternative to salmon calcitonin nasal spray, what other formulation is now available?

Injectable salmon calcitonin

What agents are under the anabolic agents?

Teriparatide Abaloparatide Romosozumab Strontium Ranelate

Teriparatide therapy is expensive, so its use is limited. However, when may it be considered as first line therapy?

Severe osteoporosis (including corticosteroid induced osteoporosis)

After teriparatide resolves the severe bone density loss, what should we follow it with?

Subsequent treatment with a bisphosphonate or denosumab is advised