Bone Mineral Homeostasis Flashcards
Teriparatide
PTH increase both osteoclasts and osteoblasts activity in bone via ligand RANKL, a TNF cytokine.
PTH couple Gs receptors to increase cAMP in bone and renal tubular cells.
High levels of PTH present continuously causes sub- periosteal bone resorption
Low dose given intermittently increases new bone formation.
Teriparatide: Recombinant PTH analog
Pulsatile doses stimulate bone formation – in the form of intermittent S.C. injection.
Whereas high doses causes resorption.
Useful in treatment of osteoporosis, provides significant intervention for restoring normal bone loss. Used for less than 2-years –due to increased risk of osteosarcoma.
AE: may cause transient hypercalcemia & hypercalciuria
Denosumab
Denosumab is a RANK Ligand (RANKL) inhibitor
It is a monoclonal antibody. It binds with RANKL and prevents it from stimulating osteoclast differentiation and function.
Inhibit bone resorption
Used in osteoporosis
AE: increased risk of infections
RANKL is on osteoblast and RANK is on osteoclast.
Calcitriol
Acts by activating steroidal nuclear receptor. Deficiency causes rickets in children and osteomalacia in adults.
Vitamin D - dependent Rickets:
Type I –defective 1α hydroxylase enzyme - ↓calcitriol ↓Ca & ↓PO4
Type II – defective receptor for Vitamin D
Calcitriol is approved for the treatment of secondary hyperparathyroidism in patients with chronic renal disease and liver disease or in dietary deficiency.
Calcipotriol is approved for the treatment of psoriasis (topical application).
Vitamin D supplements are used in osteoporosis, chronic renal failure, nutritional rickets due to inadequate dietary intake, chronic liver disease.
Adverse Effects: chronic over dose leads to hypercalcemia and hyperphosphatemia
Sevelamer
Sevelamer: It is a phosphate binding drug used to prevent hyperphosphatemia in patients with chronic renal failure. Binds to dietary phosphate and prevents its absorption in GI.
Calcium Preparations
Oral: Ca carbonate, Ca citrate, and Ca lactate
I.V. Clacium gluconate for the treatement of hypocalcemic tetany
It is used to counteract overdose of Magnesium sulfate used in eclampsia.
AE: I.M. injection may cause necrosis and abscess formation. I.V. can result in thrombophlebitis.
Salmon Calcitonin
A peptide hormone
Approved for the treatment of osteoporosis and has been shown to increase bone mass and reduce spine fractures.
Salmon calcitonin has a longer half life and greater potency.
Available as injection and nasal spray.
Estrogens
Estrogens are effective in preventing the bone loss.
Useful in preventive treatment of osteoporosis in post menopausal women.
Given as hormonal replacement therapy.
Adverse effects:
– Thromboembolism
– Migraine
– Increased risk of breast and endometrial cancer.
Tamoxifen
SERMs (selective estrogen receptor modulators)
Tamoxifen: Estrogen antagonistic action in breast, while agonistic effect in bone and uterus.
Primarily used in treatment of breast cancer, has beneficial effect on bone.
AE: Increased risk of endometrial Ca and thromboembolism and hot flushes.
Raloxifene
SERMs
Raloxifene: Estrogen antagonistic action on breast and agonist at bone. Has no estrogenic effect on endometrium.
It is approved for treatment of osteoporosis in post- menopausal women.
AE: thromboembolism, hot flushes, etc.
Bisphosphonates
MOA: They inhibi tosteoclastic activity via ↓ farnesyl pyrophosphate synthesis by disrupting mevalonate pathway ↓ osteoclast H+ ATPase.
1) They bind with hydroxyapatite in the bone and 2) Reduce resorption
Oral bioavailabality less than 10%
- *a) Etidronate –not for long-term use.
b) Alendronate c) Pamidronate (Iv), d) Risedronate**
Chronic use of Etidronate & Pamidronate may result in bone malformation ↓osteoblastic activity.
Useful in treatment of osteoporosis, malignancy associated hypercalcemia, Paget’s disease of bone.
Alendronate is drug of choice for glucocorticoid- induced osteoporosis. In post menopausal along with HRT causes increase in BMD (bine mineral density)
Paget’s disease of bone is characterized by ↑turnover with extreme bone resorption and excessive bone formation.
H/O aching bone or joint pain or fractures.
It is suspected to be due to latent viral infection and association with genetic cause – chromosome 5 & 6.
Adverse Effects:
1. Erosive esophagitis due to direct irritation to esophageal lining.
Prevented by upright position after taking medication. Increase fluid intak.e
2. Etidronate associated with osteomalacia. Osteonecrosis of jaw & fractures
Cinacalcet
Cinacalcet
It activates calcium-sensing receptors in parathyroid cells, leading to decrease in PTH synthesis and release.
- Used in secondary hyperparathyroidism in chronic renal disease and hyperparathyroidism in patients with parathyroid carcinoma.
- Adverse effects: Nausea, hypocalcemia
Fluoride
Fluoride:
– Chronic exposure can lead to new bone synthesis
which is denser but brittle.
Gallium Nitrate
Gallium nitrate:
– Inhibits bone resorption, useful in cancer-related
hypercalcemia
– Nephrotoxic
Plicamycin
Plicamycin (Mithracin):
– Cytotoxic anticancer drug
– Useful in cancer-related hypercalcemia
– AE: Thrombocytopenia, Hepatic and renal toxicity
Drugs Causing Osteoporosis and Osteomalacia
Drugs causing osteoporosis
– Corticosteroids – Heparin
– Lithium
– Anastrozole – Alcohol
Drugs causing osteomalacia
– Phenytoin
– Etidronate (More than 12 months use)
