PMID- 17722968
OWN - NLM
STAT- MEDLINE
DCOM- 20080108
LR  - 20220310
IS  - 0114-5916 (Print)
IS  - 0114-5916 (Linking)
VI  - 30
IP  - 9
DP  - 2007
TI  - Safety considerations with bisphosphonates for the treatment of osteoporosis.
PG  - 755-63
AB  - Bisphosphonates are the most commonly prescribed medications for the treatment of 
      osteoporosis. Although evidence supports a good safety profile for these agents, 
      numerous tolerability issues have been associated with their use. This review 
      provides an overview of the safety issues associated with the nitrogen-containing 
      class of bisphosphonates and discusses the potential effect of these issues on 
      adherence. The review specifically considers upper gastrointestinal (UGI) adverse 
      events (AEs), renal toxicity, influenza-like illness, osteonecrosis of the jaw 
      and evidence on how to treat or prevent these events. In clinical trials, UGI 
      AEs, including severe events such as oesophageal ulcer, oesophagitis and erosive 
      oesophagitis, have been reported at similar frequencies in placebo- and 
      active-treatment arms. However, postmarketing studies have highlighted UGI AEs as 
      a concern. These studies show that a significant portion of patients are less 
      compliant with administration instructions outside strict clinical trial 
      supervision, and when oral bisphosphonates are not administered as directed, 
      patients are more likely to experience UGI AEs. Some clinical trials with oral 
      bisphosphonates have suggested that a decrease in the frequency of administration 
      may lead to improvement in gastrointestinal tolerability. In the authors' 
      experience, the issue of UGI tolerability can be minimised by explaining to the 
      patient and/or caregiver the importance of following administration instructions. 
      Intravenous (IV) bisphosphonates have been recently approved for use in 
      osteoporosis, offering an alternative regimen for patients with osteoporosis. 
      Earlier generation IV bisphosphonates (e.g. etidronate) have been associated with 
      acute renal failure. Alternatively, late-generation IV bisphosphonates (i.e. 
      ibandronate) have shown a better safety profile in relation to renal toxicity. 
      Influenza-like illness, often referred to as an acute-phase reaction, covers 
      symptoms such as fatigue, fever, chills, myalgia and arthralgia. These symptoms 
      are transitory and self-limiting and usually do not recur after subsequent drug 
      administration. Symptoms of influenza-like illness have been associated with both 
      IV and oral bisphosphonates. Osteonecrosis of the jaw has also been associated 
      with IV bisphosphonate treatment, particularly in patients treated with high 
      doses. A small number of patients with cancer and osteoporosis using oral 
      bisphosphonates have also reported this AE. As osteonecrosis of the jaw is 
      difficult to treat and is often associated with dental procedures and poor oral 
      hygiene, preventive measures seem to be the best management option for patients 
      taking bisphosphonates.Overall, the safety and tolerability profile of the 
      nitrogen-containing bisphosphonates is good, and long-term treatment does not 
      appear to carry a risk of serious AEs. By encouraging adherence to administration 
      instructions physicians can minimise certain complications, such as UGI 
      intolerability. By being aware of other potential safety issues, such as renal 
      impairment, influenza-like illness and osteonecrosis of the jaw, physicians can 
      detect these AEs early in the course of treatment.
FAU - Strampel, William
AU  - Strampel W
AD  - Michigan State University College of Osteopathic Medicine, East Lansing, Michigan 
      48824-1316, USA. William.Strampel@hc.msu.edu
FAU - Emkey, Ronald
AU  - Emkey R
FAU - Civitelli, Roberto
AU  - Civitelli R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - New Zealand
TA  - Drug Saf
JT  - Drug safety
JID - 9002928
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Diphosphonates)
RN  - KM2Z91756Z (Risedronic Acid)
RN  - M2F465ROXU (Etidronic Acid)
RN  - UMD7G2653W (Ibandronic Acid)
RN  - X1J18R4W8P (Alendronate)
SB  - IM
MH  - Acute-Phase Reaction/chemically induced
MH  - Administration, Oral
MH  - *Alendronate/adverse effects/therapeutic use
MH  - *Bone Density Conservation Agents/adverse effects/therapeutic use
MH  - *Diphosphonates/adverse effects/therapeutic use
MH  - Etidronic Acid/adverse effects/*analogs & derivatives/therapeutic use
MH  - Female
MH  - Gastrointestinal Diseases/chemically induced
MH  - Humans
MH  - Ibandronic Acid
MH  - Injections, Intravenous
MH  - Jaw Diseases/chemically induced
MH  - Osteonecrosis/chemically induced
MH  - Osteoporosis, Postmenopausal/*drug therapy/mortality
MH  - Renal Insufficiency/chemically induced
MH  - Risedronic Acid
RF  - 58
EDAT- 2007/08/29 09:00
MHDA- 2008/01/09 09:00
CRDT- 2007/08/29 09:00
PHST- 2007/08/29 09:00 [pubmed]
PHST- 2008/01/09 09:00 [medline]
PHST- 2007/08/29 09:00 [entrez]
AID - 3093 [pii]
AID - 10.2165/00002018-200730090-00003 [doi]
PST - ppublish
SO  - Drug Saf. 2007;30(9):755-63. doi: 10.2165/00002018-200730090-00003.