18 Bone metabolism Flashcards
18.01 ANTIRESORPTIVE DRUGS
Bisphosphonates: alendronate, zoledronate, pamidronate, risedronate - actions
decrease bone resorption and increase bone density
18.01 ANTIRESORPTIVE DRUGS
Bisphosphonates: alendronate, zoledronate, pamidronate, risedronate - MOA
anchor to cell surface proteins on osteoclast membrane by prenylation
prevent osteoclast-mediated bone resorption
incorporated into the bone matrix and ingested by osteoclasts, promoting osteoclast apoptosis
18.01 ANTIRESORPTIVE DRUGS
Bisphosphonates: alendronate, zoledronate, pamidronate, risedronate - abs/distrib/elim
alendronate, ibandronate, risedronate: given orally with a large amount of water 30min before eating
IV formulations of ibandronate, zoledronate and pamidronate are available
about 50% of absorbed drug accumulates at sites of bone mineralisation, where it remains absorbed onto hydroxyapatite crystals, potentially for months or years, until the bone is resorbed
the free drug is excreted unchanged by the kidneys
18.01 ANTIRESORPTIVE DRUGS
Bisphosphonates: alendronate, zoledronate, pamidronate, risedronate - clinical use
prevention and treatment of osteoporosis
hypercalcaemia
advanced malignancies with bone metastases
pain relief in Paget’s disease of bone
18.01 ANTIRESORPTIVE DRUGS
Bisphosphonates: alendronate, zoledronate, pamidronate, risedronate - adverse effects
GIT disturbances, particularly oesophagitis (patient should remain upright for 30min after administration to reduce reflux)
bone pain
osteonecrosis of the jaw (rare) - zoledronate is most potent and more likely to cause osteonecrosis (dental checks and remedial dental work are prerequisites)
atypical femoral fractures with long-term treatment
18.02 ANTIRESORPTIVE DRUGS
Selective oestrogen receptor modulators (SERMs): raloxifene - actions
agonist effects on bone and on the CVS but antagonist action on mammary glands and the uterus
18.02 ANTIRESORPTIVE DRUGS
Selective oestrogen receptor modulators (SERMs): raloxifene - MOA
like the oestrogens, it inhibits the cytokines that recruit osteoclasts
18.02 ANTIRESORPTIVE DRUGS
Selective oestrogen receptor modulators (SERMs): raloxifene - abs/distrib/elim
given orally
undergoes first-pass metabolism
bioavailability ~2%
plasma half-life ~32h
18.02 ANTIRESORPTIVE DRUGS
Selective oestrogen receptor modulators (SERMs): raloxifene - clinical use
prophylaxis for postmenopausal osteoporosis and breast cancer
18.02 ANTIRESORPTIVE DRUGS
Selective oestrogen receptor modulators (SERMs): raloxifene - adverse effects
risk of thromboembolism
18.03 ANTIRESORPTIVE DRUGS
Calcitonin - actions
lowers serum calcium levels and decreases bone resorption
18.03 ANTIRESORPTIVE DRUGS
Calcitonin - MOA
decreases calcium and phosphate reabsorption in the kidney
inhibits bone resorption by binding to a specific receptor on osteoclasts, inhibiting their action
18.03 ANTIRESORPTIVE DRUGS
Calcitonin - abs/distrib/elim
given by SC/IM injection or nasal spray
plasma half-life 4-12 min
action lasts several hours
18.03 ANTIRESORPTIVE DRUGS
Calcitonin - clinical use
hypercalcaemia
Paget’s disease
prevention of postmenopausal osteoporosis
18.03 ANTIRESORPTIVE DRUGS
Calcitonin - adverse effects
GIT disorders
facial flushing
taste disturbances
dizziness
muscle pain
18.04 ANTIRESORPTIVE DRUGS
Monoclonal antibody: denosumab - actions
inhibits osteoclast formation, function and survival, thereby decreasing bone resorption in cortical and trabecular bone
18.04 ANTIRESORPTIVE DRUGS
Monoclonal antibody: denosumab - MOA
recombinant human monoclonal antibody (IgG2) that inhibits RANKL, the primary signal for bone resorption
18.04 ANTIRESORPTIVE DRUGS
Monoclonal antibody: denosumab - abs/distrib/elim
given by SC injection every 6 months
18.04 ANTIRESORPTIVE DRUGS
Monoclonal antibody: denosumab - clinical use
osteoporosis
can also be used for prevention of skeletal adverse events in patients with bone metastases from solid tumours, as well as to treat bone loss in patients who are receiving hormone-ablation therapy
18.04 ANTIRESORPTIVE DRUGS
Monoclonal antibody: denosumab - adverse effects
altered bowel habit, dyspnoea, hypocalcaemia, hypophosphataemia, infection, rash, osteonecrosis of the jaw (rare)
18.04 ANTIRESORPTIVE DRUGS
Monoclonal antibody: denosumab - special notes
calcium and vitamin D deficiencies need to be corrected
dental work before treatment to reduce risk of osteonecrosis of the jaw
18.05 ANABOLIC AGENTS
Recombinant form of parathyroid hormone: teriparatide - actions
anabolic effects on bone, increasing bone mass, structural integrity and strength
18.05 ANABOLIC AGENTS
Recombinant form of parathyroid hormone: teriparatide - MOA
stimulation of new bone formation by direct effects on osteoblasts indirectly increasing intestinal absorption of calcium and increasing tubular reabsorption of calcium and excretion of phosphate by kidney
reduces osteoblast apoptosis
18.05 ANABOLIC AGENTS
Recombinant form of parathyroid hormone: teriparatide - abs/distrib/elim
given SC once daily
half-life ~1h
18.05 ANABOLIC AGENTS
Recombinant form of parathyroid hormone: teriparatide - clinical use
osteoporosis in postmenopausal women and in men
glucocorticoid-induced osteoporosis
due to concerns regarding long-term safety and efficacy, maximum treatment duration should be 24 months and should not be repeated
18.05 ANABOLIC AGENTS
Recombinant form of parathyroid hormone: teriparatide - adverse effects
GIT disturbances, dizziness, arthralgia, headache
18.06 VITAMIN D PREPARATIONS
Ergocalciferol, alfacalcidol, calcitrol - actions
ergocalciferol is a prehormone that gives rise to true hormones, calcifediol and calcitriol, needed in calcium and phosphate homeostasis and in bone metabolism
alfacalcidol is converted rapidly in the liver to 1,25-dihydroxyvitamin D (metabolite of vitamin D, which acts as a regulator of calcium and phosphate metabolism)
18.06 VITAMIN D PREPARATIONS
Ergocalciferol, alfacalcidol, calcitrol - MOA
calcifediol and calcitriol act on receptors belonging to the steroid superfamily of receptors to increase serum calcium by increasing calcium and phosphate absorption from the intestine and decreasing their excretion by the kidney
18.06 VITAMIN D PREPARATIONS
Ergocalciferol, alfacalcidol, calcitrol - abs/distrib/elim
given orally
it needs bile salts for absorption
18.06 VITAMIN D PREPARATIONS
Ergocalciferol, alfacalcidol, calcitrol - clinical use
ergocalciferol: rickets, osteomalacia, hypocalcaemia caused by hypoparathryroidism
alfacalcidol and calcitrol: osteodystrophy of chronic renal failure
18.06 VITAMIN D PREPARATIONS
Ergocalciferol, alfacalcidol, calcitrol - adverse effects
excessive intake can cause hypercalcaemia
if this persists, renal calculi may result
serum calcium levels should be monitored
