Bone Mineral Homeostasis

List the Fx of:

• PTH

• Vit. D

• Calcitonin

Parathyroid Hormone (PTH) Function:

• Promotes release of calcium and phosphate into extracellular fluid.

• Increases tubular reabsorption of calcium.

• Stimulates bone remodeling.

• Increase excretion of inorganic phosphate

• Stimulates production of 1 ,25-dihydroxy-vitamin D3 by kidney

Vitamin D

• Increases GI absorption of calcium + phosphate

• Decreases renal excretion of calcium and phosphorus.

• Augments bone mineral mobilization.

• Increases renal calcium reabsorption

• May inc. Bone Formation

Calcitonin

• Inhibits osteoclast activity and osteolysis

  • Binds to osteoclasts-alters calcium passage.

• Decreases renal reabsorption of calcium.

• Increases renal excretion of calcium

• Secretion stimulated by gastrin

Describe Hypercalcemia

• Criteria?

• Primarily occurs due to:

• Endocrine/Drug Related:

• Clinical Presentation

• Criteria:

  • > 10.5 mg/dL.

• Primarily occurs due to:

  • Increased Bone resorption

  • Increased GI absorption

  • Decreased Kidney elimination 

• Endocrine/Drug Related:

  • Hyperparathyroidism

  • Malignancy

  • Vitamin D intoxication

  • Thiazides

• Clinical Presentation

  • Fatigue

  • Mental confusion

  • Nausea

  • Anorexia

  • Polyuria

  • Cardiac conduction abnormalities

Treatment of Hypercalcemia

Treatment of Hypercalcemia

• Volume expansion (rehydration) w/ normal saline

  • (200-300 ml/hr)

• Loop diuretics -> Ca Excretion

  • (furosemide)-40-80 mg IV every 1 to 4 hours

• Short term calcitonin 

  • In CHF or Renal Dysfx pt.

  • 4 units/kg every 12 hrs

• Bisphosphanates

  • Fx:

    • Inhibition: bone resorption + Osteoclasts formation 

  • Members

    • Pamidronate: 30-90 mg IV (2-24 hrs)

    • Etidronate: 7.5 mg/kg IV (over 2 hours)

    • Zoledronate: 4-8 mg IV (over 15 mins)

  • CI in Renal Insufficiency

Describe Hypocalcemia

• Criteria

• Causes

• Clinical Presentation

• Tx

Hypocalcemia

• Criteria:

  • <8.5 mg/dL

• Causes:

  • Hypoparathyroidism-absent PTH

  • Ineffective PTH

  • Reduced dietary vitamin D intake

  • Chronic kidney disease

• Clinical Presentation:

  • Muscle spasms

  • Seizure

  • Respiratory arrest

  • Laryngeal spasm

  • Irritability

---

Treatment of Hypocalcemia

• Elemental calcium (100-300 mg) IV over 5 to 10 minutes:

  • calcium gluconate

  • calcium chloride

• Oral calcium:

  • calcium carbonate

  • calcium lactate

• Calcitriol

Describe Osteoporosis

• What is it?

• Causes?

• Role of Estrogen in Bone Homeostasis:

Osteoporosis

What is it?

• Metabolic bone disease

  • Reduction of bone density

  • Increased resorption

  • Reduced calcium

  • Increased incidence of fractures

---

Causes:

• Age-related

• Hypogonadism

• Chronic glucocorticoid administration

• Post-menopausal 

  • (decreased estrogen levels)

• Calcium deficiency

---

Role of Estrogen in Bone Homeostasis:

• Increases marks of Osteoblast Dif

  • collagen type 1, osteoclacin, osteopontin

• Decreases #/Act. Of Osteoclasts

• Increases production of antiresorptive factors

  • (IGF-I , bone morphogenin protein-6)

Describe Paget’s Disease

• What is it?

• Symptoms?

Paget’s Disease

• What is it?

  • Disordered bone remodeling

    • Increased resorption + erratic and poor formation.

• Symptoms:

  • Bowing, stress fractures, arthiritis

List the Agents Affecting Calcium Homeostasis

What is a calcimimetics

Agents Affecting Calcium Homeostasis

• Teriparatide [Forteo]

• Calcitonin (Salmon) [Fortical, Miacalcin]

• Ergocalciferol [Calciferol]

• Doxercalciferol [Hecterol]

• Calcitriol [Rocatrol]

---

Calcimimetics

• Cinacalcet [Sensipar]

Describe the med. use of Calcitonin

• Forms

• Indications

• PK

• AE

Calcitonin

• Forms:

  • Calcitonin -Human (Gibacalcin):

  • Calcitonin —Salmon (Calcimar):

• Indication:

  • Paget's disease

  • Adjunctive treatment of hypercalcemic emergencies

• PK:

  • Administered SC or 1M.

  • Metabolized in kidneys

  • Cautious use in renal impairment

  • Contraindicated in the history of allergies.

• AE:

  • Headache

  • Weakness

  • Nausea

  • Vomiting.

Describe Vitamin D

• Forms

• Indications

• Forms:

  • 1 ,25 Dihydroxyvitamin D3 (Calcitriol)

  • Vitamin D2 (Ergocalciferol)

  • Doxercalciferol (Hectrol)

• Clinical indications:

  • Rickets: prophylaxis & cure

  • Osteoporosis-prevention & treatment

  • Osteomalacia

Describe Calcitriol

• Effects:

• Indications:

• CI

• PK:

Describe Ergocalciferol

• Effects

• Indications

Describe Doxercalciferol

• What is it?

• Effects

• Indications

• Caution

• PK

Calcitriol

• Effects:

  • Increases absorption of calcium in G.I tract.

  • Increases renal calcium reabsorption

  • Elevation in plasma calcium

  • Reduces PTH levels.

  • Reduces bone resorption

• Indications:

  • Hypocalcemia

  • Hypoparathyroidism

• CI

  • hypercalcemia 

  • Patients on cardiac glycosides

• PK:

  • Well absorbed from G.I tract

  • Duration:3-5 days

  • Metabolized in liver.

---

Ergocalciferol

• Effects:

  • Increased intestinal reabsorption

  • Enhances calcium mobilization

• Indicated for:

  • Hypophosphatemia

  • Osteomalacia

  • Osteoposrosis

  • Prophylaxis and treatment of rickets

---

Doxercalciferol

• What is it?

  • Vitamin D2 analog

• Effect:

  • Increases GI absorption of calcium 

• Indications:

  • hyperparathyroidism

• Caution:

  • Renal or hepatic dysfunction 

  • Pregnancy

• PK:

  • Undergoes liver activation

Describe Cinacalcet (Sensipar)

• MOA

• Indications

• PK

Cinacalcet (Sensipar)

• MOA:

  • Mimics effects of ionized calcium on calcium sensing receptor of parathyroid gland

    • Increased Ca sensitivity 

    • Reduces PTH secretion

• Indications:

  • Hypercalcemia in parathyroid carcinoma

• PK:

  • Half life: 30-40h

  • Highly bound to plasma proteins

Describe Teriparatide

• MOA

• Indication

• PK

Teriparatide

• MOA:

  • Recombinant form of PTH

    • Stimulates osteoblastic act. + bone formation 

    • Significant effects in increasing density.

    • Reduces Fracture Risk

• Indication:

  • osteoporosis in women and men.

• PK:

  • Administered parenterally (20ug/d)

Describe Denosumab

• MOA

• Indications

• CI

Denosumab

• MOA:

  • Human IgG monoclonal antibody

    • Inhibits RANKL ligand

    • Inhibition of osteoclast maturation

• Indications:

  • Postmenopausal osteoporosis

• CI:

  • Hypocalcemic patients

Pharmacological Management of Osteoporosis

Pharmacological Management of Osteoporosis

• Calcium: 

• Vitamin D2 or D3: 2

• Bisphosphanates:

  • Alendronate: 

  • Risedronate:

  • Ibandronate.

• Selective estrogen receptor modulators:

  • Raloxifene (Evista)

• Calcitonin: 

• Teriparatide: 

• Testosterone (used in men):

  • Androderm: 

  • Androgel:

  • Testoderm: