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



Original Text by Clifford R. Wheeless, III, MD.

Last updated by Clifford R. Wheeless, III, MD on Wednesday, September 4, 2013 8:38 pm