Bisphosphonates adverse effects

The most common bisphosphonate adverse effects are nausea, abdominal pain, and dyspepsia. Esophageal, gastric, or duodenal irritation, perforation, ulceration, or bleeding may occur when administration directions are not followed or when bisphosphonates are prescribed for patients with contraindications. The most common adverse effects of IV bisphosphonates include fever, flu-like symptoms, and local injection-site reactions. Osteonecrosis of the jaw occurs rarely if it develops, oral chlorhexidine washes, systemic antibiotics, and systemic analgesics are used based on severity. 

Bisphosphonates have been shown to be highly effective in osteoporosis, cancer bone metastasis, multiple myeloma, and Paget s disease of bone. While generally very well tolerated, these drugs do have potential adverse effects. Recently, the association of long-term high dose bisphosphonate treatment with osteonecrosis of the jaw has been described. This is a potentially serious side effect seen mostly in patients with multiple myeloma or... 

Several studies have evaluated the long-term efficacy and safety of bisphosphonates in postmenopausal women. One study evaluated the use of alendronate over a 10-year period and found no difference in adverse effects between women who received alendronate for 10 years and women who discontinued alendronate after 5 years. Women who discontinued alendronate after 5 years continued to experience sustained increases in bone mineral density compared with baseline values and a reduction... 

Proper drug administration is important for optimal absorption and prevention of adverse effects. Oral bisphosphonates... 

Raloxifene exerts an estrogen-like effect on bone, while acting as an estrogen antagonist in the uterus and breast tissue (p. 254). In terms of fracture prophylaxis, its effectiveness appears inferior to that of bisphosphonates. Thromboembolism and edema are reported as adverse effects. 

Other bisphosphonates, such as etidronate and pamidro-nate, have caused both reversible and irreversible auditory, visual, and olfactory hallucinations beginning 2 hours to 1 week after drug administration. The mechanism of these adverse effects is unknown but is thought to be independent of calcium homeostasis. 

Adverse effects of the bisphosphonates include low-grade transient fever and headache other effects are asymptomatic hypocalcemia, hypophosphatemia, and hypomagnesemia (5-7). 

Adami S, Zamberlan N. Adverse effects of bisphosphonates. A comparative review. Drug Saf 1996 14(3) 158-70. 

Consistent with the preclinical observations, all i.v. bisphosphonates have the potential to affect renal function in clinical use however, renal adverse effects appear to be dependent on the baseline renal status of the patient and the dosing regimen. Although the incidence of renal adverse events is infrequent when i.v. bisphosphonates are administered at their recommended doses and infusion rates, monitoring of renal function is advisable in aU patients receiving i.v. bisphosphonate therapy [29-34]. Attempts to compare the renal safety profiles of different bisphosphonates are confounded by limited head-to-head comparisons between different bisphosphonates. Although limited... 

Tlie clinical utility of another first-generation, non-nitrogen-containing bisphosphonate, tiludronate, has been limited because of concern over renal adverse effects observed in early trials. In a dose-finding study for the treatment of HCM, 19 patients received i.v. drug followed by oral maintenance therapy [70]. Three patients had elevated serum creatinine levels after i.v. drug administration of 4.5 or 6.0 mg/kg, 1 of whom developed acute renal insufficiency and subsequently died, most probably due to tiludronate, although renal infection and allopurinol therapy could have played a contributory role. 

Zoledronic acid 4 mg as a single intravenous infusion once yearly Effects on bone turnover and bone density were similar to those with daily oral bisphosphonates. Efficacy against fractures has not yet been established. Adverse effects include myalgia and pyrexia. 

Most patients prefer once-weekly bisphosphonate administration (see Table 88-6). This dosing schedule lowers G1 tract drug exposure. Because the turnover rate of the cells lining the G1 tract is about 5 days, any cells damaged during drug exposure are theoretically replaced before the next week s dose is taken. Once-weekly alendronate administration achieved similar BMD results, had similar GI adverse effects, and did not impair mineralization, compared with daily doses of 10 mg. ... 

Teriparatide contains the first 34 amino acids in human parathyroid hormone and represents a novel approach to osteoporosis treatment. Although hyperparathyroidism leads to bone loss (see Fig. 88-3), therapeutic doses (for shorter periods of time) conversely improve BMD and rednce fractnre risk. Parathyroid hormone is currently the only approved osteoporosis medication that works by stimulating bone formation. Becanse of adverse effects and cost concerns, teriparatide is reserved for treating those at high risk of osteoporosis-related fracture who cannot or will not take or have failed bisphosphonate therapy. 

Diel, I. J., Bergner, R., and Grotz, K. (2007). Adverse effects of bisphosphonates Current issues. /. Support. Oncol. 5, 475-482. 

Tanvetyanon, T. and Stiff, P. (2006). Management of the adverse effects associated with intravenous bisphosphonates. Ann. Oncol. 17,897-907. 

Antipsychotic drugs metabolic adverse effects (Chapter 6) Bisphosphonates osteonecrosis of the jaw (Chapter 49)... 

Bisphosphonates must be administered carefully to optimize the clinical benefit and minimize the risk of adverse GI effects. All bisphosphonates are... 

I Administration. Even under optimal conditions, all bisphosphonates are poorly absorbed (bioavailabihty = 1% to 5%). Bisphosphonates must be administered carefully to optimize the chnical benefit and minimize the risk of adverse G1 effects. Each oral tablet should be taken with at least 4 ounces of plain tap water (not coffee, juice, mineral water, or milk) at least 30 minutes before consuming any food or any other supplement or medication. The weekly oral solution needs to be taken with only 2 ounces of water. The patient should remain upright (either sitting or standing) for at least 30 minutes after bisphosphonate administration. When calcium and vitamin D dietary consumption are insufficient, supplementation is needed to ensme the beneficial effects of bisphosphonates. 

The adverse side effects of bisphosphonates are renal toxicity, acute-phase reactions, gastrointestinal toxicity, hypocalcemia, ocular complications, asthma erythema, phlebitis, altered taste, and central nervous system side effects. The osteonecrosis of the jaw is the emerging one (Diel et ah, 2007 Tanvetyanon and Stiff, 2006). To overcome this kind of problem, researchers are now turning toward nature-based drugs. 

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