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Bisphosphonates

- See: osteoporosis and hypercalcemia


- First Generation Bisphosphonates:
- short chain molecules which inhibit the Krebs cycle;
- types:
- etidronate
- clodronate

- Second Generation:
- long chain molecules which inhibit fatty chain pathways;
- types:
- pamidronate
- available in IV form;
- alendronate
- 0.7% absorption;

- Third Generation:
- risedronate:
- 6% absorption;
- zolendronate
         - available in IV form which can be given on an annual basis;
  - protocol:
                 - if the serum 25-hydroxyvitamin D level is less than 15 ng per milliliter then patients receive a loading dose of either vitamin D3 or D2 (at
a dose of 50,000 to 125,000 IU given orally or intramuscularly) 14 days before first infusion;
- all patients received daily supplementation with oral calcium (1000 to 1500 mg) and vitamin D (800 to 1200 IU)
- exclusion criteria:
                            - previous hypersensitivity to a bisphosphonate
- calculated creatinine clearance of less than 30 ml per minute
- corrected serum calcium level of more than 11.0 mg/deciliter (2.8 mmol per liter) or less than 8.0 mg /deciliter (2.0 mmol / liter);
- active cancer
- metabolic bone disease other than osteoporosis
- life expectancy of less than 6 months in the investigator's judgment


- references:
- Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis.
- Treatments for Osteoporosis — Looking beyond the HORIZON.


Complications:
- renal effects
: nephrocalcinosis renal insufficiency
hypocalcemia: total serum Ca monitored first and third days following infusion of the bisphosphonate;
AVN:
- Bisphosphonates and oral cavity avascular bone necrosis: a review of twelve cases.
- Bisphosphonate-induced avascular osteonecrosis of the jaws: a clinical report of 11 cases.
- Does avascular necrosis of the jaws in cancer patients only occur following treatment with bisphosphonates?
- Osteonecrosis of the Jaw — Do Bisphosphonates Pose a Risk?
- Uveitis


Images in clinical medicine. Bisphosphonate-associated contact stomatitis.

Atraumatic bilateral femur fracture in long-term bisphosphonate use.

Low vitamin D related to decreased response to bisphosphonates