Chapter 61: Calcium Levels And Bone Mineralization Flashcards
Calcium
Functions and daily requirements
Critical to function of the skeletal, nervous, muscular, and cardiovascular systems
Body stores
Bones: More than 98% stored in the bones
Blood: Total serum calcium = 10 mg/dL
Absorption
Occurs in the small intestine
Increased by parathyroid hormone and vitamin D
Glucocorticoids decrease absorption
Excretion
Calcitonin augments calcium elimination
Regulation of calcium levels
Absorption from the small intestine
Excretion by the kidney
Resorption in bone
Regulated by
Parathyroid hormone
Vitamin D
Calcitonin
PTH
Promotes calcium resorption from bone
Promotes tubular reabsorption of calcium that had been filtered by the kidney glomerulus
Promotes activation of vitamin D, and thereby promotes increased absorption of calcium from the intestine
Recommended dietary intake of Ca
0-6m 200-1000 mg
6-12m 260-1500 mg
1st 3 yr of life between 700-2500mg
4-8y ~1000mg
9-18y 1300mg
19-50y ~1000mg
51-70y M 1-2000, F 1200-2500 mg
>70 1200-2000 mg
Vit d
Increases calcium resorption from bone
Decreases calcium excretion by the kidney
Increases calcium absorption from the intestine
Important regulator of calcium and phosphorus homeostasis
Health benefits
Found helpful in preventing CV disease, DM, some autoimmune disorders
Calcitonin
Released from the thyroid gland when calcium levels in the blood rise too high
Lowers calcium levels by inhibiting resorption of calcium from bone and increasing calcium excretion by the kidney
Does not influence calcium absorption
Hypercalcemia
Usually asymptomatic
If symptoms are present: Kidney, gastrointestinal (GI) tract, CNS
HyperCa causes
Cancer
Hyperparathyroidism
Vitamin D intoxication
Sarcoidosis
Use of thiazide diuretics
HyperCa tx
Drugs that promote urinary excretion of calcium
Drugs that decrease mobilization of calcium from bone
Drugs that decrease intestinal absorption of calcium
Drugs that form complexes with free calcium in the blood
IV saline
Then diuresis with a loop diuretic
HyperCa drugs
Edetate disodium
Glucocorticoids
Calcitonin
Bisphosphonates
Gallium nitrate
Cinacalcet (Sensipar): Suppresses parathyroid hormone (PTH) secretion; used for hypercalcemia associated with hyperparathyroidism
Hypocalcemia
Increases neuromuscular excitability
Clinical presentation
Tetany, convulsions, and spasm of the pharynx
HypotCa cases
Deficiency of PTH
Deficiency of vitamin D
Deficiency of calcium
Chronic renal failure
Long-term use of certain medications, such as magnesium-based laxatives, and drugs used to manage osteoporosis (e.g., bisphosphonates and denosumab)
HypoCa tx
Intravenous calcium supplementation (calcium gluconate)
Once calcium levels have been restored: Calcium citrate for maintenance
Vitamin D
Rickets
Vitamin D deficiency results in reduced calcium absorption
PTH is released
PTH restores serum calcium by promoting calcium resorption from bone, thereby causing bones to soften
Stress on softened bones caused by bearing weight results in deformity
Treatment: Vitamin D replacement therapy
Osteomalacia (adult counterpart of rickets)
Absence of vitamin D
Impaired mineralization of bone
Bowing of the legs
Fractures of the long bones
Kyphosis (“hunchback” curvature of the spine)
Diffuse, dull, aching bone pain
Treatment: Vitamin D replacement therapy
Hypoparathyroidism
Cause: Inadvertent removal of parathyroid glands during surgery on the thyroid gland
Lack of PTH: Hypocalcemia, paresthesias, tetany, skeletal muscle spasm, laryngospasm, convulsions
Treatment: Calcium supplements and vitamin D
Primary hyperparathyroidism
Cause: Usually results from a benign parathyroid adenoma
Increase in PTH secretion: Hypercalcemia and hypophosphatemia
Skeletal muscle weakness, constipation, CNS symptoms, renal calculi, bone abnormalities
Treatment: Surgical resection of parathyroid glands; calcium-lowering drugs—cinacalcet [Sensipar]
Secondary hyperparathyroidism
Cause: Common complication of chronic kidney disease (CKD)
High levels of PTH and disturbances of calcium and phosphorus homeostasis
Treatment
Vitamin D sterol (e.g., paricalcitol) and calcium-containing phosphate-binding agents
Cinacalcet [Sensipar]: Can reduce PTH and has a positive effect on calcium and phosphorus levels
Calcium salts oral
Mild hypocalcemia, dietary supplements
PMS
Colorectal adenoma
Adverse effects: Hypercalcemia
Drug interactions: Corticosteroids, tetracycline, fluoroquinolone, thyroid hormone, phenytoin, bisphosphonates, loop diuretics, thiazide diuretics
Parental Ca salts
Parenteral: Calcium chloride and calcium gluconate
Adverse effects: Highly irritating; do not give IM; can cause IV extravasation
Drug interaction: Digoxin
Vit d for deficiency
Vit D25 hydroxy 30-60 nanograms per mL
To treat deficiency:
<1y ~2000 iu/day
1-18y ~4000 iu/day
>19 up to 10,000 iu/day
Types of vit D
Ergocaliferol [Calciferol Drops, Drisdol] -> vit D2. Found in plants. Used in prescriptions drugs and fortifying foods.
Cholecalciferol -> vit D3. This is the vit d that is produced in humans when skin is exposed to sunlight
No differences with biological effects of vit d2 and vit d3
First 2 are dietary supplements. Vit d3 is preferred.
Calcitriol (1,25-Dihydroxy-D3)
Doxercalciferol [Hectorol]
Paricalcitol [Zemplar]
Calcitonin-salmon
Vitamin D toxicity
Early symptoms: Weakness, fatigue, nausea, vomiting, anorexia, abdominal cramping, constipation
Later symptoms: Kidney function is affected, resulting in polyuria, nocturia, and proteinuria
Neurologic: Seizures, confusion, ataxia
Cardiac dysrhythmia
Coma
Calcium deposition in soft tissues
Decalcification of bone
Seen in infants with > 1000 iu/day
Seen in adults with > 50,000 iu/day
Tx -> d/c vit d and increase IVF
Drugs for Disorders Involving Calcium
Calcium salts
Vitamin D
Calcitonin-salmon [Calcimar, Miacalcin, Fortical]
Bisphosphonates
Alendronate, risedronate, ibandronate, tiludronate, etidronate, zoledronate, pamidronate
Calcitonin
Inhibits the activity of osteoclasts
Decreases bone resorption
Inhibits tubular resorption of calcium
Increases calcium excretion
Therapeutic uses: Osteoporosis, Paget disease, hypercalcemia
Adverse effects: nausea, flushing of face and hands, intranasal dryness
Bisphosphonates
Structural analogs of pyrophosphate
Incorporate into bone: Inhibit bone resorption by decreasing activity of osteoclasts
Indications: Postmenopausal osteoporosis, osteoporosis in men, glucocorticoid-induced osteoporosis, Paget disease of bone, hypercalcemia of malignancy
May also help prevent and treat bone metastases in patients with cancer
Adverse effects: May include ocular inflammation, osteonecrosis of the jaw (ONJ), atypical femur fractures, atrial fibrillation (A-fib)
-monitor jaw pain
Alendronate [Fosamax, Fosamax Plus D]
Most widely used oral bisphosphonate
Uses: Postmenopausal osteoporosis, male osteoporosis, glucocorticoid-induced osteoporosis, Paget disease of bone
Oral bioavailability: Poor
Adverse effects: Generally safe; esophageal ulceration, atypical femoral fracture, esophageal cancer, musculoskeletal pain, ocular problems, ONJ, hyperparathyroidism, A-fib
Don’t want pt to eat or drink until 30 min after med
Wait 2 hr to take any Ca products or any other mineral supplements
Risedronate [Actonel]
Uses: Postmenopausal osteoporosis, male osteoporosis, glucocorticoid-induced osteoporosis, Paget disease of bone
Adverse effects: Arthralgia, diarrhea, headache, rash, nausea, flulike syndrome, esophagitis, atypical femoral fractures, ocular problems, musculoskeletal pain
Take in morning
Delayed release form -> they can eat
Ibandronate [Boniva]
Uses: Prevention and treatment of postmenopausal osteoporosis
Dosing:Once a month or once every 3 months
Adverse effects: GI effects, including esophagitis, dyspepsia, abdominal pain; ocular inflammation; atypical fractures; ONJ; renal damage if IV administered too rapidly
Oral dosing on empty stomach in the morning with full glass of water an stay upright for 60 min after
If given IV, needs to be slow admin
Tiludronate [Skelid]
Use: Paget disease of bone
Adverse effects: Nausea, diarrhea, dyspepsia, esophagitis, ocular problems, musculoskeletal pain, possibly esophageal cancer, chest pain, edema, paresthesias, hyperparathyroidism, vomiting, flatulence
Raloxifene [Evista]
Structurally similar to estrogen and binds to estrogen receptors
Comparison to estrogen
Therapeutic uses
Osteoporosis
Breast cancer
Adverse effects
Thromboembolic events, such as deep vein thrombosis (DVT), pulmonary embolism, stroke, and fetal harm, weight gain
Daily tablet
Teriparatide [Forteo]
Form of PTH
Treat GIOP –glucocorticoid induced OP
Produced by recombinant DNA
Only drug that increases bone formation
Generally well tolerated
Nausea, headache, back pain, leg cramps
Denosumab [Prolia, Xgeva] indications
First-in-class RANKL (RANKL, receptor activator of nuclear factor kappa-B ligand) inhibitor with three indications:
Osteoporosis in postmenopausal women and in men at high risk for fractures
Bone loss in women and men receiving certain anticancer therapy
Prostate or breast cancer
Prevention of skeletal-related events in patients with bone metastases from solid tumors
Treat GIOP
Denosumab ADR
Hypocalcemia
Serious infections
Dermatologic reactions
Dermatitis, eczema
Osteonecrosis of the jaw
Wary about dental implants and dental procedures
Denosumab admin
Prolia store in fridge an warm this ~15-30 min at room temp before admin. Should be clear an colorless or very pale yellow. Any cloudiness –do not Admin
Cinacalcet [Sensipar]
Calcimimetic drug
Approved for primary hyperparathyroidism and secondary hyperparathyroidism (caused by CKD)
Increases the sensitivity of calcium-sensing receptors to activation by extracellular calcium
Suppresses PTH secretion
Adverse effects: Nausea, vomiting, diarrhea, hypocalcemia
Drugs for Hypercalcemia
Furosemide
Promote renal excretion of Ca
Glucocorticoids
Decrease intestinal absorption of Ca
Bisphosphonates
Decrease bone reabsorption by osteoclasts
Inorganic phosphates
Decrease plasma levels of Ca
Edetate disodium
Chalating agent
Bind with Ca to ensure renal excretion occurs
Osteoporosis
Most common disorder of calcium metabolism
Low bone mass and increased bone fragility
OP seen with aging
typically in women –small boned, small frame women. Can also be seen small framed men
Weight bearing exercise offset OP
Primary prevention
Calcium, vitamin D, lifestyle
Diagnosis
Measurement of bone mineral density (BMD)
Dual-energy x-ray absorptiometry (DEXA)
Effects ~ 10 million Americans
~34 million have reduced bone mass
Common fx sites: vertebrae (spinal), distal forearm around the wrist, femoral neck (hip)
Treating Osteoporosis in Women
Agents that decrease bone resorption: Estrogen, raloxifene, bisphosphonates, calcitonin, denosumab; sufficient calcium and vitamin D are important
Agent that promotes bone formation: Teriparatide (Forteo)
Agents that reduce fractures: Teriparatide, denosumab, zoledronate
Treat anyone with hip or vertebrae fx, OP t score of </= -2.5 at the femoral neck or spine, someone who presents with low bone mass –t score between -1 and -2.5 at the femoral neck or spine, 10-year probability of hip Fx of 3% or more, a 10 year probability of another OP factor
* based on USA adapted Frax calculations
Treating Osteoporosis in Men
Five drugs have been approved for osteoporosis treatment in men:
Alendronate [Fosamax]
Risedronate [Actonel]
Zoledronate [Reclast]
Teriparatide [Forteo]
Denosumab [Prolia]
2 million men
3 million at risk
