1. kidney: Ca² excretion↓ P excretion ↑, synthesis of vit D 2. bone: osteoclast and osteoblast stimulation 3. intestine: Ca² and P absorption ↑ (indirect effect mediated by vit D) net effect: Ca² ↑ P ↓

A.15 bone mineral homeostasis Flashcards by שני דוידפור

what are the primary hormonal modulators of bone mineral homeostasis?

parathyroid hormone (PTH)
Vitamin D

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what are the secondary hormonal modulators of bone mineral homeostasis?

calcitonin, estrogens, glucocorticoids

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what are the non-hormonal modulators of bone mineral homeostasis?

Bisphosphonates
RANK-ligand inhibitors
Calcimimetics
Fluoride

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what is Teriparatide and how is it given?

PTH analogue, SC injection

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what is the indication for teriparatide?

osteoporosis

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SE of teriparatide?

hypercalcemia, hypercalcuria

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function of PTH

kidney: Ca² excretion↓ P excretion ↑, synthesis of vit D
bone: osteoclast and osteoblast stimulation
intestine: Ca² and P absorption ↑ (indirect effect mediated by vit D)

net effect: Ca² ↑ P ↓

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function of Vitamin D

kidney: Ca² and P reabsorption↑
bone: direct effect–> bone resorption ↑serum Ca² and P
intestine: Ca² and P absorption↑
inhibit PTH release

net effect: Ca² ↑ P ↑

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what do vitamin d2 and d3 require that calcitriol (active form) doesn’t?

metabolism in liver or kidney to become active

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analogue of calcitriol

doxercalciferol
paricalcitol
calcipotriene

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which vitamin D drug is given topically?

calcipotriene

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indications for Ergocalciferol (Vit D2) and Cholecalciferol (Vit D3) ?

vitamin D deficiency- rickets disease, osteomalacia, nutritional deficiency, hypoparathyroidism, nephrotic syndrome

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SE of Ergocalciferol (Vit D2) and Cholecalciferol (Vit D3)

hypercalcemia, hyperphosphatemia, hypercalcuria

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indications for calcitriol

secondary hyperparathyroidism in patients with chronic kidney disease
hypocalcemia in patients with hypoparathyroidism

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indications for Doxercalciferol and paricalcitol?

secondary hyperparathyroidism in patients with chronic kidney disease
(milder SE than calcitriol)

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indication for calcipotriene

psoriasis

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function of calcitonin

Kidney: Ca² and P excretion↑
inhibits osteoclast activity–>↓ bone resorption

net effect: Ca²↓
CALCITONIN –>tones down the Ca² level, keeps it in the bones.

how is calcitonin given?

SC, nasal spray

indications for calcitonin

osteoporosis
paget’s disease
hypercalcemia- acute management

SE of calcitonin

rhinitis with the nasal spray, hypocalcemia

What is Raloxifene and what is it’s function

SERM- selective estrogen receptor modulator

inhibits PTH-induced bone resorption by inhibiting osteoclast activity

indication for raloxifene

post-menopausal osteoprosis

SE of Raloxifene

hot flushes, ↑ risk of venous thromboembolism

glucocorticoids function

intestinal and renal Ca² absorption↓
RANK-L stimulation
inhibit osteoblast and collagen synthesis

what risk is there in prolonged use of GC?

osteoporosis (in systemic therapy)

name 2 bisphosphonates

Alendronate Zoledronate Risedronate

what is the function of bisphosphonates?

1. direct suppression of osteoclast activity | 2. increase of bone mineral density in the first year of use

how is alendronate given?

oral or parenteral

indications for alendronate, zoledronate?

osteoporosis (1st line treatment) Paget's disease bone metastasis hypercalcemia due to hyperparathyroidism

SE for bisphosphonates?

hypocalcemia, upper GI irritation, osteonecrosis of the jaw (rare, with IV use)

what is Denosumab and how is it given?

RANK-ligand inhibitor human monoclonal antibody (IgG) SC injection every 6 months

what is the function of denosumab?

inhibit RANK-L stimulation of osteoclast activity--> ↓ bone resorption

indication of denosumab?

Post-menopausal osteoporosis

SE of denosumab

increased risk of infection

what is Cinacalcet and how is it given?

it's a calcimimetic (mimics the action of Ca² on tissues) activates Ca² sensing receptor--> ↓PTH--> ↓ Ca² given orally

indications for Cinacalcet

secondary hyperparathyroidism due to chronic kidney disease | parathyroid carcinoma management

SE of Cinacalcet

nausea, hypocalcemia

risk factors for developing primary osteoporosis

endocrine: hypothyroidism, Type 1 DM GI: malabsorption, vitamin D and C deficiency Drug-induced: anticoagulants, chemotherapy , alcohol

what is osteoporosis?

reduction of the bone strength that leads to an increased risk of fractures (vertebal and hip mostly)

how do we measure bone mineral density?

DEXA scan - dual energy X-ray absorptiometry | graded based on the T score

classification of BMD (based on T score)

normal: -1.0 or greater osteopenia: between -1.0 and -2.5 osteoporosis: -2.5 or less severe osteoporosis: -2.5 or less with a pathologic fracture

pharmacological management of osteoporosis

1. SERM- Raloxifene 2. Bisphosphonate 3. RANK-L inhibitors (denosumab) 4. calcitonin analogues 5. PTH analogues 6. Ca² supplementation 7. Vitamin D supplementation 8. thiazide diuretics