- Clinical science
Bisphosphonates (e.g., etidronate, alendronate) are used for the treatment of hypercalcemia and bone metabolism disorders, such as osteoporosis or tumor-induced osteolysis. All bisphosphonates primarily slow down the degradation of bone substance by interfering with osteoclast function. However, nitrogen-containing bisphosphonates work by a different molecular pathway than simple bisphosphonates and have a stronger effect. Important side effects of bisphosphonate therapy include hypocalcemia, renal impairment, and aseptic osteonecrosis of the jaw. Therefore, bisphosphonates are contraindicated in patients with hypocalcemia and those with a limited glomerular filtration rate (GFR). Additionally, oral bisphosphonates may cause esophageal damage while IV bisphosphonates can induce flu-like symptoms.
Bisphosphonates bind to hydroxyapatite binding sites on the surface of bone tissue → uptake by osteoclasts during phases of bone resorption → interference with osteoclast function and promotion of osteoclast apoptosis→ reduced bone resorption
- Simple bisphosphonates (tiludronate, etidronate) : reduction of osteoclast proton production, suppression of osteoclast maturation and recruitment, and promotion of osteoclast apoptosis
- Nitrogen-containing bisphosphonates (alendronate, risedronate, zoledronate): inhibition of the enzyme farnesyl pyrophosphate synthase → disturbance of osteoclast metabolism and signaling → reduced osteoclast function and promotion of osteoclast apoptosis
- Also inhibit mineralization
- Additionally: prevention of osteoblast apoptosis and inhibition of osteocyte apoptosis
The nitrogen-containing bisphosphonates have a stronger effect than the simple bisphosphonates!
Bisphosphonates also reduce bone formation since bone resorption and formation are intrinsically connected! However, bone resorption is reduced more severely than bone formation!
- and (hypocalcemia can also lead to osteomalacia, see )
- Aseptic osteonecrosis of the jaw: mostly in high-dose IV administration in tumor patients, but can also occur with oral administration and in other patients
- Atypical fractures (particularly of the femur)
- Musculoskeletal pain
- Renal impairment
- Ocular inflammation and visual disturbances
- Oral bisphosphonates; (alendronate, risedronate, etidronate, tiludronate): esophageal inflammation and cancer
- IV bisphosphonates (zolendronate); : acute-phase reaction with flulike symptoms; (e.g., fever, joint, and muscle pain) 24–72 hours after administration
Bisphosphonates should be taken in the morning with sufficient water and in an upright position at least 60 minutes before eating!
We list the most important adverse effects. The selection is not exhaustive.
- Tumor-induced osteolysis
- Hereditary skeletal disorders