Thiazide Diuretics in Treatment of Osteoporosis

The study discussed looked at the ability of thiazide diuretics to increase bone density. This is not an FDA labelled use but in theory the mechanism of action of the drug corresponds to increased calcium reabsorption (in the process of increasing sodium and water excretion). LaCroix and colleagues looked at its use in this manner.

The study looked at 205 women and 115 men all between the ages of 60 and 79 who were not antihypertensive nor did they have osteoporosis. A double blind study in which participants received a daily dose of 12.5 mg hydrochlorothiazide (HCTZ), 25 mg HCTZ or a placebo was used to evaluate this. They were to take their assigned medication once by mouth daily for three years. They would check in with monthly appointments to have their blood pressure monitored since the medication of course has an effect on lowering blood pressure. Also every 6 they would have their bone densities examined using an x-ray densitometer.

The results of this study showed a slight (but significant) difference in the change in bone density in the 25 mg group and the placebo group after 36 months. There was a greater reduction in bone density in the group that was taking the placebo than the other two groups, while there was not a significant difference in the reduction in bone density between the group taking the higher dose of HCTZ than the group taking the lower dose. While the 25 mg group had seen a 0.61% increase in bone density, the placebo group had seen 0.32% decrease in bone density.

The results of this study showed that hydrochlorothiazide could assist in slowing the reduction in bone density in older patients. It may not do this in a way that would make this medication an appropriate monotherapy; however it may have a place a adjunctive therapy alongside calcium/vitamin D supplementation and in more serious cases bisphosphonates.


LaCroix A, Ott S, Ichikawa L, et al. Low-dose hydrochlorothiazide and preservation of bone mineral. Ann Intern Med. 2000;133(7):516-26.

Ann Intern Med. 2000;133(&):516-26

Blog Officially Open: Safety of Off-Label Medication Use

Eguale and colleagues conducted a study to monitor and evaluate the off-label use of prescription medications and adverse drug events (ADE) in adults. The authors conducted a prospective cohort study of adult patients who visited a primary care physician in Quebec, Canada who participated in the Medical Office of the XXIst Century (MOXXI) research program and received a prescription for a medication between January 1, 2005 and December 30, 2009. The MOXXI physicians use an electronic health record (EHR) that integrates beneficiary, medical and pharmacy claims information together. The EHR requires that the physician document the indication for the medication, reasons for dose modifications and discontinuations and details related to any ADE. Indications were considered off-label if they were not approved by Health Canada (Canada’s FDA equivalent). A drug information database was used to classify the level of evidence supporting the use of the medications for the off-label indications. Strong evidence was defined as medication effective or favorable efficacy for off-label indication, medication is recommended for most patients with indication, and there are studies of efficacy, including at least one randomized controlled trial. In brief, the study included 46,021 patients who received 151,305 prescriptions of which 11.8% were prescribed off-label. The indication for use was not supported by strong evidence 80.9% of the time. The overall incidence of ADEs for all medications was 13.2 per 10,000 person-months. There was a 44% increase in risk of ADEs when medications were used off-label compared with on-label use. There were higher rates of ADE when the off-label use lacked strong evidence. The authors noted that the elderly and patients who frequent physicians may be overrepresented in their data. The authors concluded that the off-label use of medications is a risk factor for ADE.

JAMA Intern Med. 2016;176(1):55-63

Off-label use of medications is complicated. The editorial that accompanies the Eguale paper discusses some of in the issues, including the potential changes to off-label promotion of medications, the allowance of prescribers to write for off-label medication use, and the lack of surprise of the study’s results. How can EHRs in the US become more sophisticated and user friendly to allow for more clear documentation of off-label use of medications to allow for more thoughtful intervention? How can pharmacists help with the safe and effective use of medications, particularly when off-label use is being considered?