Bisphosphonates - An Overview

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Bisphosphonates - An Overview

Bisphosphonates are the drug of choice for Osteoporosis & Paget's disease of Bone.

Bisphosphonates (also called diphosphonates) are a class of drugs that prevent the loss of bone mass.

Used in the treatment of many skeletal disorders-

ØBone metastases,

Øosteoporosis,

ØPaget’s disease etc.

Mechanism of Action :

•Bisphosphonates are used to inhibit bone resorption & they act through different mode of actions:

1.Inhibit development of osteoclasts. Induction of osteoclast apoptosis.

2.Reduction of osteoclast activity.

3.Prevention of development of osteoclasts from hematopoietic precursors.

4. Stimulation of production of an osteoclast inhibitory factor.

There are two types of Bisphosphonates :

Non nitrogen containing BPs are taken up by the osteoclast and cause cell apoptosis through activation of capsase pathway.

Nitrogen containing BPs are not metabolised and affect protein prenylation of osteoclast by inhibiting farnesyl diphosphate (FPP) synthase, a key enzyme of the mevalonate pathway .

•The inhibition of bone resorption can be explained largely by cellular mechanisms.

• Can be considered at three levels: tissue, cellular, and molecular.

•The effect may be directly on the osteoclasts and may be mediated, via other cells such as osteoblastic lineage cells and macrophages.

Indications :

1.Postmenopausal

2.Glucocorticoid-induced osteoporosis,

3.Paget’s disease,

4.Osteolytic and osteoblastic bone metastases,

5.Fibrous dysplasia,

6.Heterotopic ossification,

7.Myositis ossificans.

8.Other bisphosphonates, medronate and oxidronate are mixed with radioactive technetium and are injected for imaging bone and detecting bone disease

Bisphosphonates in Metastatic disease :

1.They controlhypercalcemia,

2.Reduce bone pain,

3.Reduce the number of pathologicfractures,

4.Prolong survival.

Intravenous zolendronate and palmindronate are the ones most useful and should be combined with either chemotherapy or hormonal therapy in women with metastatic bone disease.

Zolendronate is the first bisphosphonate shown to be effective in both lytic and blastic metastatic disease

Side Effects of Bisphosphonates :

•Upset stomach

•Inflammation/erosions of esophagus

•Fever/flu-like symptoms

•Slight increased risk for electrolyte disturbance

•Uveitis

•Musculoskeletal joint pain

•Bisphosphonate related osteonecrosis of jaw (BRONJ)

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