Osteoporosis Flashcards
What is bone comprised of?
Calcium and Phosphate
Protein meshwork
Collagen Matrix
Cells- Osteoblasts, osteoclasts, osteocytes
What do bones function to do?
Provide support
Enables us to carry out various physiological processes such as respiration and movement
In homeostasis of calcium and phosphate
What is serum calcium controlled by?
Parathyroid hormone (PTH) derived from the parathyroid glands
What do high plasma calcium concentrations do to PTH? Low plasma calcium concentrations?
High plasma calcium concentration suppress PTH secretion
Low plasma calcium concentration stimulates PTH secretion
What are the functions of PTH?
Maintains serum calcium
Acts on the kidney to reabsorb calcium from the tubular filtrate
Stimulates kidney to convert 25-OH-VitD to 1,25-(OH)2-VitD (calcitriol)
Directly on bone to mobilize calcium
What is endogenous (skin)?
Cholecalciferol (Vit D3)
What is exogenous (diet)?
Ergocalciferol (Vit D2)
Where are cholecalciferol and ergocalciferol stored and metabolized?
Endogenous (skin) = cholecalciferol (Vit D3) or exogenous (diet) = ergocalciferol (Vit D2) stored or metabolized in liver to 25-OH-VitD then 1,25-(OH2)-VitD which promotes intestinal absorption of calcium
Where does calcitonin come from and what does it do?
From the thyroid gland
In response to high calcium and inhibits resorptive activity of osteoclasts
What must be present in the intestines in order for calcium to be absorbed?
Vitamin D
What is osteopenia?
Early signs of osteoporosis
1 to 2.5 standard deviations below bone mass of a normal young adult
What is osteoporosis?
(Osteo)=Bone; (Porosis)=Porous
It is 2.5 or more standard deviations below the bone mass of a normal young
What is primary osteoporosis?
Postmenopausal women
Senile occurs with age, usually > 70 years of age in men and women
What is secondary osteoporosis?
Occurs in people who have other conditions
Hyperthyroidism, steroid use, chronic kidney disease (hyperparathyroidism), smoking, excessive ETOH
Often seen in younger people
What is the normal bone density T score?
T score of greater than -1.0
What is bone mineral density T score for osteopenia?
T score of less than or equal to -1.0 but greater than -2.5
What is the bone mineral density T score for ostepenic + other risk factors?
T score less than -2.0 or less than -1.5 with other risk factors for fracture.
What is the bone mineral density T score for osteoporosis?
Hx of fragility fracture or a BMD T score less than or equal to -2.5 at any site (lumbar spine, femoral neck, greater trochanter, or total hip
What are the modifiable risk factors for osteoporosis?
Inadequate Calcium Intake Inadequate Vitamin D Intake Excess protein in diet Diet Alcohol use (chronic) --can cause poor nutrition --increased glucocorticosteroid secretion and decreased sexual function-all leading to bone loss. --Alcohol may also directly affect cell function. Sedentary Lifestyle Carbonated Drinks Smoking Anorexia
What are the non-modifiable risk factors of osteoporosis?
Parathyroid hormone problems
Thyroid hormone excess
Family history and genetics– Late age menarche, Early menopause (< 45years),Early surgical menopause, Low testosterone in males
Depression
Steroid use: patients taking glucocorticoids are 2x more likely to have a hip fracture and 4-5x more likely to have a fracture in the spine.
Long-term heparin, Lithium, Anticonvulsants, Thiazolidinediones
Drugs altering Ca absorption or elimination
Lack of Ovarian Function (menopause, surgery, cancer therapies)
Body Size-small thin bone women-this is one case where more weight is better. (< 128lbs)
Caucasian, Asian, Hispanic ethnicity
What are the drugs that may be associated with reduced bone mass in adults?
Aluminum Anticonvulsants (phenobarbital, phenytoin) Cytotoxic drugs Glucocorticosteroids and adrenocorticotropin Gonadotropin-releasing hormone agonists Immunosuppresants Lithium Long-term heparin use Progesterone, parenteral, long-acting Supraphysiologic thyroxine doses Tamoxifen (premenopausal use) Total parenteral nutrition
Who should be tested for osteoporosis?
All Women aged 65 or older.
Women age > 60 with risk factors.
Younger postmenopausal women with one or more risk factors, (OTHER THAN BEING FEMALE).
Men aged 70 or older
May consider screening Men > 50 with risk factors
What is done for the prevention of osteoporosis?
Maximize peak bone mass
Adequate calcium intake
Adequate vitamin D intake
When should an infant be supplemented with Vit D?
If they are exclusively or partially breastfed: IU/Day
Who should be treated for osteoporosis?
Postmenopausal women and men ≥50 yrs
Hip or vertebral fracture
T-score≤ -2.5 at femoral neck or spine after excluding secondary causes
Low bone mass (T-score -1.0 to -2.5 at femoral neck or spine)
10-year probability hip fracture ≥ 3%
OR
10-year probability major osteoporosis fracture ≥ 20%
What are the nondrug treatments that reduce bone loss in postmenopausal women?
Diet
Smoking cessation
Physical activity
What are the diet components that reduce bone loss in postmenopausal women?
High in calcium and Vit D High in fruits and vegetables Moderate protein Avoid sodas High amounts of whole grains
What are the physical activity components that reduce bone loss in postmenopausal women?
Exercise, activity—weight bearing exercises Running Walking Weight training Swimming—very little effect
What are the pharmacological agents used for treatment of osteoporosis?
Calcium Vitamin D Teriparatide Bisphosphonates Calcitonin Raloxifene Estrogen Denosumab
Calcium- types and MOA
Calcium gluconate IV/PO Calcium carbonate PO- this is tums Calcium lactate PO Calcium citrate PO- available in a liquid form Calcium chloride IV MOA: Replace calcium deficiencies
Calcium-indications
Hypocalcemia
Calcium deficiency
Osteoporosis or osteopenia
Calcium- Contraindications and ADRS
Contraindications
Hypercalcemia
ADRs GI disturbances Constipation Bradycardia Arrhythmias
Calcium- Monitor
Monitor calcium levels if given IV
Usually about q 6 hrs
Vitamin D- inactive and active form and MOA
Inactive form—ergocalciferol (requires kidneys and liver to function to convert to active form)
Active form–calcitriol
400-800 I.U. daily
Calcium-Vit D combo available
MOA: Acts on the gut to absorb calcium from the diet
Vitamin D- ROA and Indications
ROA: Oral, IV, UV reaction in skin
Indications Hypocalcemia Vitamin D deficiency Postmenopausal osteoporosis Renal failure- require primarily active form due to struggle with converting the inactive form.
What do anabolic agents do?
Stimulate bone formation
Directly stimulate formation by effects on osteoblast function and lifespan
What do antiresorptive agents do?
Inhibit bone resorption
Decreased osteoclastic bone resorption.
Teriparatide (Forteo)- MOA and indications
MOA-Recombinant parathyroid hormone
Stimulates osteoblastic activity
Only used when:
History of osteoporotic fractures
Multiple risk factors and Failed/intolerant to other therapies
THis is not first line but only should be used when patient already has a fx or has failed other therapies. Very expensive
Teriparatide (Forteo)- contraindications and adverse effects
Contraindications:
Paget’s disease, increased alkaline phosphatase, h/o radiation treatment
Adverse effects:
Dizziness, leg cramps
Transient increase in serum calcium
BLACK BOX WARNING: OSTEOSARCOMA
Bisphosphonates
Approved products:
Fosamax (alendronate) PO; tx and prevention (once a week)
Actonel (risedronate) PO; tx and prevention (once a week)
Boniva (ibandronate) PO; tx and prevention (once a month)
Zometa (zoledronic acid) IV; tx hypercalcemia of malignancy
Reclast (zoledronic acid) IV; tx osteoporosis (Aug 2007) (once a year 15min infusion)
Bisphosphonates- MOA
works by inhibiting bone resorption via:
Inhibits osteoclastic proton pump necessary for dissolution of hydroxyapatite
Decreased osteoclastic formation/activation
Increased osteoclastic apoptosis
Bisphosphonates- efficacy and indications
Efficacy
Increase BMD
Decrease both vertebral and nonvertebral fractures
Indications
Prevention and/or treatment of osteoporosis (men/women)
Prevention of corticosteroid-induced osteoporosis
Management of hypercalcemia of malignancy
Bisphosphonates- disadvantages and cautions/contraindications
Disadvantage of oral—must take 30 minutes before a meal and remain upright at least 30 minutes.
Cautions/ Contraindications
Renal impairment/ Hypocalciemia
Contraindicated CrCl < 30-35ml/min (renal impairment)
Alendronate (Fosamax)
Bisphosphonate
Therapeutic effects sustained over 10 year period; D/C results in gradual loss of effects
ADRs
GI: Nausea, diarrhea, abdominal pain
Esophageal erosions
Hypocalcemia and hypophosphatemia (transient)
Zoledronic Acid (Reclast)
Bisphosphonate
5mg IV infusion over 15 minutes once a year
Pretreat with APAP
Must be properly hydrated prior to infusion to prevent renal impairment
ADRs
Acute phase reactions: N/V, HA, myalgias, pyrexia, flu-like symptoms
Osteonecrosis of jaw, Afib, ocular “-itis”
What is the biggest difference b/w alendronate and zoledronic acid?
Alendronate is given PO and zolendronic acid is given IV. Due to Alendronate being given PO it is more corrosive to the esophagus
Calcitonin (Miacalcin)-MOA
Derived from salmon
MOA: calcitonins are hypocalcemic hormones secreted by the parafollicular cells of the human thyroid gland
Excreted in response to elevated serum calcium concentrations
Calcitonins increase mineral stores in bone
Decreases the number & activity of osteoclasts
In kidney, decreases tubular reabsorption of sodium and calcium (hypercalcemia)
Calcitonin (Miacalcin)- function
Also improves bone architecture, relieves pain, increases function
Calcitonin (Miacalcin)- ROA and indications
ROA: Intranasal, SubQ
Indications Hypercalcemia Paget’s disease of the bone Bone pain in metastatic disease Bone pain in osteoporosis
Calcitonin (Miacalcin)- ADRs
N/V/D
Flushing
Tingling in the hands
Nasal irritation (if given intranasally)
What are the advantages of calcitonin nasal spray?
Do not have to remain upright
Do not have to avoid eating
What are the disadvantages of calcitonin nasal spray?
Is not as good at rebuilding bone
Must remember which nare medication was placed previous day.
Tolerance with continued use
Must keep refrigerated
Raloxifene- MOA
Selective Estrogen Receptor Modulator Substances (SERMS)
Evista (raloxifene)
MOA:
It acts like an estrogen in the bone like an estrogen antagonist in the breast and uterus.
It increases bone mineral density in both spine and femoral neck
Decreases serum LDL
Does not stimulate endometrial growth. (doesn’t affect the breasts)
Decreases vertebral fractures 30 – 50%
Evista (raloxifene)- indications
When to use: 1st line if patient postmenopausal and contraindication to bisphosphonates
Evista (raloxifene)- ADRs
Chest pain and peripheral edema
Venous thromboembolism (3.4 fold risk) and pulmonary thromboembolism (2 fold risk)
Hot flashes
Weight gain
Estrogen- MOA
- FDA labeled indication for treatment and prevention of osteoporosis (4th line)
Suppresses transcription of IL-6 that induces osteoclast proliferation, differentiation and activation
Promotes apoptosis of osteoclasts
Estrogens clearly slow the rate of bone loss in postmenopausal women
Some studies document an INCREASE in bone density
Estrogen- Disadvantages
If family history of breast cancer more risk for breast cancer
Intact uterus will need progesterone as well,
Breast tenderness and enlargement,
Increased risk of blood clots, CV events
Denosumab- MOA
Monoclonal antibody
Slows bone breakdown but also entire bone remodeling process
Twice yearly injection at the office
Very expensive
Denosumab- indications
Postmenopausal women with osteoporosis and high risk of fracture (that is, previous fracture due to osteoporosis or multiple fracture risk factors).
Patients with osteoporosis for whom other osteoporosis treatments have failed.
Patients who cannot tolerate other osteoporosis treatments
Denosumab-ADRs
Decreased Calcium levels- must replace calcium
Back pain
Pain in the extremities
Muscle and bone pain
High cholesterol levels
Bladder infections- these can be very problematic in the elderly post-menopausal women
Possible increased risk of serious infections
