Osteoporosis Flashcards
Osteoclast vs osteoblast
Osteoclast (resorption of bone)
Osteoblast (rebuilding of bone)
When does osteoporosis occur?
When there is an imbalance in the osteoclast and osteoblast function
- bone formation does not replace resorption
What is a major contributor to an increased risk of osteoporosis in older female patients?
Menopause
What BMD T-score defines osteoporosis?
BMD T-score ≤−2.5
What does this score indicate?
2.5 standard deviations below a normal young adult reference
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
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)
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
What tool is good for identifying fracture risk?
Fracture risk assessment tool (FRAX)
What tool is good for identifying bone density?
CAROC system
How can therapeutic choices for osteoporosis be divided into?
Prevention and treatment
Which population is prevention therapy particularly important for?
Patients on chronic corticosteroid therapy
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
How should the nutritional supplement of calcium be managed?
Diet first, and then supplement if necessary
Is calcium supplementation associated with increased risk of CV events?
No. Recent data has refuted this claim.
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.
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.
What agents are used to treat osteoporosis?
Antiremodelling or antiresorptive agents
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
Which drug class in the mainstay of osteoporosis treatment?
Bisphosphonate
Which drugs are under the bisphosphonate drug class?
Alendronate
Risedronate
IV zoledronate
Bonus: What must be corrected prior to initiating therapies like Prolia or Jubbonti?
Hypocalcemia
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
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
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?
No
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.
2
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
3
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?
No
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
