Calcium & Vit D
- Can it prevent or treat osteoporosis alone?
a. Which calcium preparation is probably the best?
b. Vitamin D levels have to be Adequate for what?
- NO! Adequate Ca2+ intake is needed for any other Tx to work!
a. Chewable
b. for Optimal Absorption of Calcium
blah
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Hormone Drugs
Calcitonin
a. When is it secreted?
b. Decreases Circulating Ca2+: how?
c. Will maintain bone in what 2 times? Stimulated by what?
- Bone Pain/Loss; Bone Density; Osteoporotic Fractures?
- Adverse Effects?
- Pharmacokinetics?
- Indications?
- a. Circulating Ca2+ is too high
b. Inhibits Osteoclasts to Decrease Resorption
c. in PREGNANCY and LACTATION (stimulated by estrogen) - Decrease; Increase; Decrease
- Can cause Allergic RxNs; Nasal RHINITIS/SINUSITIS —> Nasal Spray; Nausea and Vomiting –> Injection
- Nasal Spray and Injection
- Osteoporosis (Not 1st Line) and Paget’s Disease
Hormone Drugs
TERIPARATIDE
a. What is it?
b. What does PTH Stimulate?
c. What PRODUCES BONE GROWTH?
- Indications?
- Pharmacokinetics
- Adverse Effects
- CIs
- a. RECOMBINANT PTH
b. REMODELING, causing bone resorption and new bone formation
c. INTERMITTENT ADMINISTRATION! - Tx for Osteoporosis and Hypoparathyroidism
- Subcutaneous Injection (Intermittent: Once or Twice a Day)
- Hypercalcemia and Hypercalciuria; Injection site Reactions; Dizziness and Leg Cramps
- OSTEOSARCOMA (black label).
Hormone Drugs
Estrogen and Progestin
Estrogen Helps prevent Post-menopausal development of Osteoporosis
Hormone Drugs
Raloxifene
?????
Bisphosponates
ALENDRONATE, Ibandronate, Zoledronic Acid
a. What are they?
b. FDA approved?
- a. PCP bond analogs of Pyrophosphate. Powerful drugs used in HIGH RISK FRACTURE PATIENTS
b. No.
*ALENDRONATE: Take Orally: Poor ABSORPTION; 2 Hrs before Breakfast, w/o Ca2+ or Mg. (taken Weekly)
Ibandronate: Take MONTHLY
*Zoledronic Acid: Injected IV Once/year
Bisphosponates
- Mech of Action
- Indication
- Pharmacokinetics?
- Inhibit Osteoclast Activity and bone Resorption; Strengthen bone.
- FIRST LINE DOC for POST-MENOPAUSAL OSTEOPOROSIS; Paget’s disease
- Oral: ABSORPTION is POOR. TAKE on EMPTY STOMACH!. only 1/2 GLASS of WATER and stay upright for 30 minutes AFTER to dECREASE ESOPHAGEAL IRRITATION!
Bisphosponates
Adverse Effects?
- CIs?
ABDOMINAL PAIN, NAUSEA, VOMITING
IV and Oral Administration increase POTENTIAL for JAW OSTEONECROSIS!
- ORAL ones DO NOT USE in Pts w/SERIOUS ESOPHAGEAL DISEASE or Pts w/BEDREST and can’t stay upright for an hour!
Rank-Ligand Inhibitors
DENOSUMAB
a. What does it stand for?
- Mechanism of Action?
- Indications
- Pharm
- Adverse Effects
- CI?
- a. Den = DENSITY; OS = Osteo; U = Human; MAB = Monoclonal Antibody
- Inhibits Bone Resorption. Antibody to RANK-L (factor made by Osteoblasts that’s needed for the formation of Mature Osteoclasts)
- SEVERE OSTEOPOROSIS in Postmenopausal women; Increase Bone mass and strength in Both cortical and Trabecular Bone
- S.C. Injection; Once/6 months
- Hypocalcemia; Cellulitis, OSTEONECROSIS of the JAW!!!! (in cancer studies)
- Absolute: HYPOCALCEMIA (fix first)
Relative: Pregnancy/Lactation; Chronic Kidney Disease; Pts at risk for serious infections
Bone Remodeling
- What is dominant?
- Goal of Osteoporosis Tx?
- Resorption Dominant
2. DECREASING BONE RESORPTION
Regulation
- PTH
a. Stimulated when?
b. How does it INCREASE Circulating Ca2+?
- a. Blood Calcium is Low
b. Increase Osteoclast Activity and Number (RANKL)
* Increased Renal Ability to REABSORB Calcium: Decreased Ca2+ Excretion and Increased PO4 Excretion.
Why? Ca2+ Cant get into the bone
*STIMULATES CALCITRIOL (Production of 1,25-dihydroxy Vitamin D)
Regulation
- Vitamin D
- Increases Circulating Ca2+: How?
- a. Stimulates COLAGEN synthesis in Osteoblasts (RANKL)
–> Stimulates Osteoclast Activity (Increased intestinal absorption and decreased renal excretion)
Works in conjunction with PTH
Risk Factors for Osteoporosis?
Postemenopausal Women; Long-Term Glucocorticoid use; Thyrotoxicosis; Alcoholism; Malabsorption Syndrome