How do bisphosphonates inhibit osteoclasts?

Mechanism of action — The bisphosphonates inhibit osteoclastic bone resorption via a mechanism that differs from that of other antiresorptive agents [2-4]. Bisphosphonates attach to hydroxyapatite binding sites on bony surfaces, especially surfaces undergoing active resorption.

Which side chain in bisphosphonates determines the Antiresorptive property?

Although the structure of the R2 side chain is the major determinant of antiresorptive potency, both phosphonate groups are required for the drugs to be pharmacologically active. Bisphosphonates are characterised by poor intestinal absorption but highly selective localisation and prolonged storage in bone.

How do bisphosphonates cause hypocalcemia?

By inhibiting bone resorption, bisphosphonates reduce calcium efflux from bone into the circulation, leading to the development of hypocalcemia. Recently, increased osteoblastic activity that leads to avid calcium uptake has been postulated as a possible mechanism of zoledronic acid induced hypocalcemia.

Why are bisphosphonates contraindicated in hypocalcemia?

Bisphosphonates (applies to Fosamax) hypocalcemia The use of bisphosphonates is contraindicated for the treatment of osteoporosis in patients with hypocalcemia. These agents increase bone mineral density, a process that requires an adequate supply of calcium in the body.

Do bisphosphonates build bone?

By slowing or stopping the bone-resorbing portion of the remodeling cycle, bisphosphonates allow new bone formation to catch up with bone resorption. Fosamax and other drugs such as Actonel, Boniva, and Reclast increase bone density and help prevent and treat osteoporosis and/or reduce the risk of fractures.

How do bisphosphonates affect dental treatment?

Bisphosphonates irreversibly alter the metabolism of the osteoclasts, so there is little or no bone resorption, even if the blood supply is good. The action of bisphosphonates that dental professionals should be concerned about is that they destroy osteoclasts, without which there is no bone healing.

Is bisphosphonates a chemotherapy?

The use of bisphosphonates to prevent bone metastases remains experimental. Last, bisphosphonates in addition to chemotherapy are superior to chemotherapy alone in patients with stages II and III multiple myeloma and can reduce the skeletal morbidity rate by approximately one half.

Why bisphosphonates is the drug of choice for osteoporosis give its advantages?

Bisphosphonate therapy normalizes bone turnover, reduces the number of bone remodeling sites and stress risers, restores the balance of bone remodeling, prevents bone loss and deterioration of bone structure and, in patients with osteoporosis, reduces fracture risk (5).

Do bisphosphonates reduce serum calcium?

In summary, although bisphosphonates lead to a decrease in serum calcium, in most patients rapidly acting homoeostatic mechanisms involving an increase in PTH secretion lead to a restoration in calcium concentrations.

How do bisphosphonates affect calcium levels?

Bisphosphonate treatment causes an early reduction in bone resorption followed by a later reduction in bone formation. The early inhibition of bone resorption induces a reduction in serum calcium which leads to increased parathyroid hormone (PTH), and subsequently an increase in 1,25-dihydroxyvitamin D.

What are the contraindications of bisphosphonates?

Contraindications to bisphosphonates include:

• History of hypersensitivity to the bisphosphonate.
• Hypocalcemia.
• Chronic kidney disease with a glomerular filtration rate of less than 30 to 35 mL/min.

Why are nitrogenous bisphosphonates not preferred?

N-containing-bisphosphonates can cause upper gastrointestinal irritation and mucosal ulceration, so patients must not lie down for 30–60 minutes after oral dosing to prevent reflux of the tablet into the esophagus, and these agents cannot be used in those with anatomical or motility disorders of the upper …

How are bisphosphonates similar to pyrophosphate in structure?

Bisphosphonates are analogues of pyrophosphate that contain a carbon instead of an oxygen atom. The P C P structure allows a great number of possible variations, especially by changing the two lateral chains on the carbon atom. Many bisphosphonates have been investigated in animals and humans with respect to their effect on bone.

How does pyrophosphate bind to hydroxyapatite crystals?

Like pyrophosphate, the bisphosphonates bind to the hydroxyapatite crystals of bone and prevent both their growth and their dissolution. The biological activity of the bisphosphonates can be modified by altering the structure of the two side chains on the carbon atom.

What are the uses of bisphosphonates in medicine?

Their principal uses are for Paget disease of bone, myeloma, bone metastases, and osteoporosis in adults, but there has been increasing and successful application in pediatric bone diseases, notably osteogenesis imperfecta. Bisphosphonates are structural analogues of inorganic pyrophosphate but are resistant to enzymatic and chemical breakdown.

How are bisphosphonates internalized in the osteoclast?

Bisphosphonates (BPs) are a class of bone-seeking agents that are selectively internalized by osteoclasts and inhibit bone resorption via two distinct mechanisms. Anke J. Roelofs, Michael J. Rogers, in Principles of Bone Biology (Third Edition), 2008 Bisphosphonates are compounds characterized by two C–P bonds.