双膦酸盐的副作用

LETTER
Respiratory complications associated with IV zoledronic acid infusion in the treatment of postmenopausal osteoporosis
H.Taggart &J.Cheng &P.Archbold
Received:31July 2009/Accepted:22September 2009/Published online:8October 2009#International Osteoporosis Foundation and National Osteoporosis Foundation 2009
Introduction
Zoledronic acid (ZA)is used to treat postmenopausal osteoporosis in a dose of 5mgs IV annually [1].We report our experience in treating 30consecutive women in 2008with postmenopausal osteoporosis.
Patients
Thirty women mean age 71.7years (range 50–85)with postmenopausal osteoporosis were studied.
Twenty-five (83%)were intolerant of oral bisphospho-nate therapy.
Results
Nine patients had pre-existing chest disease.Five of these had no respiratory problems post infusion.Six patients (two with pre-existing asthma and two with chronic obstructive pulmonary disease,COPD)had dyspnoea which was not present at the time of infusion but developed within 24h.It was described by the patient as mild in three cases and moderate in two and resolved within 3days without the need for treatment.One of these patients,a woman of 78years with pre-existing COPD,became acutely dyspnoeic about 8h post
infusion.She was admitted to hospital with type 2respiratory failure and spent a short time in ICU.She spent 3weeks in hospital but eventually recovered to her pre-morbid state.
All these adverse events have been reported to the Medicines and Healthcare Products Regulatory Agency (MHRA)in the UK and Novartis.
Discussion
Post-marketing surveillance is an important part of drug safety.Often,side effects are not detected in clinical trials but emerge later in clinical practise [2].Dyspnoea is described as “uncommon ”by the manufacturers of ZA suggesting an incidence of between 1in 100and 1in 1,000.We have found that it occurred in 20%of our patients,one of whom became seriously ill with type 2respiratory failure.
The MHRA [3]have received 19reports of dyspnoea and four of respiratory failure in patients given ZA.
The absence of a control group and the subjective nature of patients reporting of symptoms are possible weaknesses of this study.
Conclusion
In this audit,we have described dyspnoea which is a probable adverse event following closely after the admin-istration of IV zoledronic acid.One patient was hospitalised with respiratory failure.The strong temporal association makes it likely that the infusion caused the chest symptoms.While we will have to await the experience of others,we
H.Taggart (*):J.Cheng :P.Archbold Osteoporosis Clinic Belfast City Hospital,Lisburn Road,
Belfast BT97AB,UK
e-mail:hugh.taggart@
Osteoporos Int (2010)21:1621–1622DOI 10.1007/s00198-009-1088-6
would urge caution in using IV zoledronic acid in patients with pre-existing chronic chest disease.
Conflicts of interest Dr.Taggart has received reimbursement for lectures from Sanofi-Aventis,Eli Lilly,Servier,Proctor&Gamble and travel expenses from Eli-Lilly and Roche.
Dr.Archbold has received reimbursement for lectures from Roche, MSD,Servier,GSK and travel expenses from Sanofi-Aventis and Takeda.
Dr.Cheng has no conflict of interest.References
1.Black D,Delmas P,Eastell R,Reid I,Boonen S,Cauley J et al
(2007)Once yearly zoledronic acid for treatment of postmeno-pausal osteoporosis.NEJM356:1809–1822
2.Taggart HM,Alderdice J(1982)Fatal cholestatic jaundice in
elderly patients taking benoxaprofen.BMJ284:1372
3.Medicines and Healthcare Products Regulatory Agency(2009)
Drug analysis on zoledronic acid.Available via / safetyinformation.Accessed June2009
1622Osteoporos Int(2010)21:1621–1622。