Bis

Bisphosphonates

Class of drugs used to prevent the loss of bone density

Introduction

Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs for osteoporosis. Bisphosphonates are structurally similar to pyrophosphate, a naturally occurring compound in the body that inhibits bone mineralization.

Mechanism of Action

Bisphosphonates work by inhibiting osteoclast-mediated bone resorption, thereby leading to an indirect increase in bone mineral density. Osteoclasts are cells that break down bone tissue, and bisphosphonates inhibit their activity by binding to hydroxyapatite in the bone matrix. When osteoclasts attempt to resorb bone that contains bisphosphonates, they are unable to do so effectively, leading to their apoptosis.

Pharmacokinetics

Bisphosphonates have a low bioavailability when taken orally, typically less than 1%. They are poorly absorbed from the gastrointestinal tract, and their absorption is further reduced by food, calcium, and other divalent cations. Once absorbed, bisphosphonates are rapidly taken up by the bone and have a very long half-life in bone, often exceeding 10 years. They are not metabolized and are excreted unchanged by the kidney.

Clinical Uses

Bisphosphonates are primarily used in the treatment of:

• Osteoporosis
• Paget's disease of bone
• Bone metastases
• Multiple myeloma
• Hypercalcemia of malignancy

Side Effects

Common side effects of bisphosphonates include:

• Gastrointestinal issues such as nausea, abdominal pain, and esophageal irritation.
• Osteonecrosis of the jaw (ONJ), a rare but serious condition.
• Atypical femoral fractures, which are rare but have been associated with long-term use.
• Hypocalcemia, especially in patients with vitamin D deficiency or hypoparathyroidism.

Administration

Bisphosphonates can be administered orally or intravenously. Oral bisphosphonates, such as alendronate and risedronate, are typically taken weekly or monthly. Intravenous bisphosphonates, such as zoledronic acid and ibandronate, are administered less frequently, often once a year or every few months.

Contraindications

Bisphosphonates are contraindicated in patients with:

• Hypocalcemia
• Severe renal impairment
• Esophageal abnormalities that delay esophageal emptying

Monitoring

Patients on bisphosphonates should be monitored for:

• Renal function, especially in those receiving intravenous formulations.
• Calcium and vitamin D levels.
• Signs of osteonecrosis of the jaw and atypical femoral fractures.

Conclusion

Bisphosphonates are a cornerstone in the management of osteoporosis and other bone-related diseases. Their ability to inhibit bone resorption makes them effective in increasing bone density and reducing fracture risk. However, their use must be carefully monitored due to potential side effects and contraindications.

See Also

• Osteoporosis
• Bone density
• Osteoclast

External Links

• National Osteoporosis Foundation
• International Osteoporosis Foundation