Is your patient undergoing treatment with biphosphonates?

This Post is adapted from the Canadian Pharmacists Association (CPhA) Drug Monograph: Biphosphonates

Product Summary

Pharmacology

Basic structure of a bisphosphonate on top. To compare the structure of pyrophosphate below. Note the similarity in structure. Courtesy of Wikipedia (Eng)

Bisphosphonates (previously called diphosphonates) are stable analogues of pyrophosphate. After binding to bone surfaces, they slow the formation of hydroxyapatite crystals and delay their aggregation into large clusters. They also interfere with the resorptive action and promote apoptosis (programmed cell death) of osteoclasts, resulting in decreased depth and rate of formation of new bone remodeling units. Lifelong accumulation of remodeling deficits begins shortly after bone growth stops and is thought to be the underlying mechanism of age-related bone loss. By inhibiting this process, bisphosphonates increase bone mass and decrease susceptibility to fracture. An additional proposed mechanism of action is inhibition of osteocyte and osteoblast apoptosis, thereby increasing the life span of osteocytes and decreasing bone fragility.

Indications

• Bisphosphonates have many clinical uses including prevention and treatment of primary and secondary osteoporosis, Paget’s disease of bone, hypercalcemia, primary hyperparathydroidism (when surgery is not possible), multiple myeloma and osteolysis associated with bone metastases of malignant tumors.

Warnings

• Osteonecrosis of the jaw (ONJ) has been reported in patients with cancer receiving intravenous bisphosphonates. It has also been reported rarely with bisphosphonates (oral or iv) used for treatment of osteoporosis. Other risk factors risk factors include use of corticosteroids, head and neck radiotherapy or poor oral hygiene.
• The Canadian Association of Maxillofacial Surgeons recommends that all oncology patients undergo a thorough dental examination including radiographs before initiation of intravenous bisphosphonate therapy [J Rheumatol 2008;35(7):1391-7]. Ideally, any invasive dental procedure should be completed prior to initiation of high-dose bisphosphonate therapy in this patient group; they also suggest that non-urgent procedures be delayed until 3–6 months after interruption of bisphosphonate therapy. A dental examination is not required prior to starting oral or intravenous bisphosphonates for osteoporosis if the patient has good oral hygiene and appropriate dental care.
• Deterioration of renal function and acute renal failure may occur with bisphosphonates, especially when given iv. Risk factors include advanced age, dehydration and concomitant use of nephrotoxic or diuretic medications. Ensure adequate hydration prior to and following iv bisphosphonate administration. Acute kidney injury was not associated with oral bisphosphonate use in the elderly [Kidney Int 2012;82(8):903-8]. Because bisphosphonates are excreted renally, caution and appropriate monitoring are advised for patients with renal failure. Use of bisphosphonates is not recommended in patients with severe renal impairment (creatinine clearance <30 mL/min).

Precautions

• Although osteonecrosis of the jaw is more commonly seen in cancer patients receiving intravenous bisphosphonates, cases have been reported in patients taking oral therapy. 
• Because mild decreases in serum calcium and phosphorus have been observed with some bisphosphonates, maintaining adequate intake of calcium and vitamin D is recommended. Calcium interferes with the absorption and therefore should be taken at a different time of the day than the bisphosphonate.