Original Research

Bisphosphonates in the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis

Author and Disclosure Information

 

References

Safety and Tolerability

The withdrawal rates of the included studies ranged from 0% to 62% ([Table 3]). Of the dropouts reported, 42% were secondary to protocol violations or administrative reasons, and 16% were because of noncompliance. Twenty percent of study withdrawals were because of adverse events, of which 78% (29/37) were deemed not related to the treatment regimen. No significant difference was reported in dropout rates between the treatment and control groups.

In most of the studies no statistical significance concerning adverse effects was found when the treatment group was compared with the control group. Nine studies42-47,50,51 discussed the subgroup of gastrointestinal (GI) adverse events, since this has been the greatest historical concern about the use of bisphosphonates. Eight studies found no difference in overall GI effects, and one study45 reported a statistical trend for increased GI side effects with dose escalation of alendronate. This trend was probably secondary to an increase in abdominal pain in the treatment group when compared with the placebo group. In one study,46 diarrhea was more common in patients receiving 5 mg risedronate than those taking placebo (number needed to harm=15), although significance was not reported.

Discussion

The studies examining the use of bisphosphonates for the prevention or treatment of CIO are difficult to interpret because of the various bisphosphonates and regimens, the heterogenicity in populations, the effect of the underlying disease on bone, and concomitant therapeutic interventions. A review of the currently published literature suggests bisphosphonates effectively prevent vertebral bone loss in patients treated with long-term corticosteroids. Patients receiving steroids for more than 3 months (secondary prevention) gained bone mass when placed on a bisphosphonate, while patients naive to steroids (primary prevention) maintained more bone density than the control group.42-44,46,47,50,51,53 This reinforces the fact that patients taking steroids for more than 3 months have already lost bone that can be partially regained with bisphosphonate treatment. In contrast, patients given bisphosphonates who were naive to steroids did not have significant changes in BMD from baseline; this group, however, was able to maintain bone density while the control group lost bone density.

Data regarding the impact of bisphosphonates on the risk of CIO-induced fractures are sparse and inconclusive. This is not surprising since most of the trials have been of relatively short duration (<2 years), and have not been sufficiently powered to show fracture reduction. Postmenopausal women not taking estrogen seem to benefit most from using bisphosphonates for the prevention of bone loss and of vertebral fractures in CIO.

A meta-analysis of a similar set of data based on a Cochrane systematic review of published literature was reported in 1999.55 The authors state that of the small number of controlled clinical trials examining the use of bone-sparing agents in patients at risk for CIO bisphosphonates have shown some of the best evidence for reducing bone loss, particularly at the lumbar spine. They also concluded that bone density changes correlate with fracture risk in patients with CIO, but there are insufficient data to make conclusions regarding fracture risk reduction and use of bisphosphonates.

Overall, adverse effects of the bisphosphonates were minimal, and no statistical significance was found in studied populations when compared with control groups. However, the incidence of GI adverse events with alendronate may be as high as 15% in clinical practice, despite low incidence rates in phase III trials, possibly because of administration errors.56 Directions for use are the same for all oral bisphosphonates, and include staying upright and not eating for at least 30 minutes after administration. Because oral bioavailability is usually less than 5% even on an empty stomach, bisphosphonates should be taken with a full glass of water in the morning after an overnight fast.11,56,57

Implications for further research

Although current evidence supporting bisphosphonate use documents efficacy in BMD changes and trends toward reduced vertebral fracture risk in the treatment of CIO, more research is clearly desirable. The recent FDA approval of alendronate and risedronate has highlighted the need for aggressive measures to prevent and treat CIO. More research is needed in large studies to assess vertebral and nonvertebral fractures. Head-to-head comparative trials of bisphosphonates with other pharmacologic options, such as hormonal therapy or calcitonin are essential to establish evidence-based clinical guidelines. Studies addressing combination therapy with bisphosphonates and HRT in postmenopausal women would also be useful. Finally, comparative studies of the various bisphosphonates in relation to one another are needed. These synthetic pyrophosphate analogs possess a broad range of potencies, selectivity, and adverse effect profiles. Because each bisphosphonate has unique biological, chemical, and physiochemical properties, the results of one bisphosphonate study cannot be extrapolated to other compounds within the same drug class.3,56,58,59 Differences in study design, patient populations, and other confounding variables also prevent the assumption of a class effect with certain research findings. This distinction becomes especially important with the new bisphosphonates on the horizon (clodronate, tiludronate, ibandronate, and zoledronate).

Pages

Recommended Reading

Liquid Medication Dosing Errors
MDedge Family Medicine
Childhood Cancer Survivors and Primary Care Physicians
MDedge Family Medicine
Does coffee protect against the development of Parkinson disease (PD)?
MDedge Family Medicine
Does the addition of mouth-to-mouth ventilation to chest compressions improve survival in bystander treatment of cardiac arrest?
MDedge Family Medicine
Does nefazadone alone, the cognitive behavioral-analysis system of psychotherapy, or the combination of both work best for patients with chronic depression?
MDedge Family Medicine
Is electron-beam computed tomography (EBCT) a reliable tool for predicting coronary outcomes in an asymptomatic population?
MDedge Family Medicine
Do African American asthmatics perceive and describe their asthma symptoms differently than white asthmatics?
MDedge Family Medicine
Is losartan superior to captopril in reducing all-cause mortality in elderly patients with symptomatic heart failure?
MDedge Family Medicine
Is there a clinical difference in outcomes when b-agonist therapy is delivered through metered-dose inhaler (MDI) with a spacing device compared with standard nebulizer treatments in acutely wheezing children?
MDedge Family Medicine
Is there a simple and accurate algorithm that clinicians can use to more effectively select women for bone densitometry testing?
MDedge Family Medicine