Difficult Choices in Long-term Osteoporosis Management

SOURCE: Leder BZ, et al. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): Extension of a randomised controlled trial. Lancet 2015;386:1147-1155.

The propriety of long-term bisphosphonate utilization (that is, > 5 years) has recently come into question subsequent to a clinical trial that compared bisphosphonate discontinuation at 5 years vs continuation for 10 years. Despite a decline in bone mineral density (BMD) in the cessation group, the actual hip fracture rate was no greater than in the group that continued bisphosphonate for 10 years. Since there are adverse effects and expense associated with treatment, many questions remain about how long to treat and which agent(s) to utilize.

In the DATA (Denosumab and Teriparatide Administration) trial, postmenopausal women (n = 94) with osteoporosis were randomized to treatment with teriparatide (TER), denosumab (DEN), or both for 2 years. DATA-Switch is an extension of DATA, during which patients on monotherapy were switched (e.g., if on DEN for 2 years, switched to TER, and vice versa), and patients on dual therapy (DEN + TER) were switched to DEN monotherapy. The SWITCH phase of the trial lasted an additional 2 years. TER patients switched to DEN, and DEN + TER patients switched to DEN monotherapy continued to accrue more mass at the lumbar spine, distal radius, femoral neck, and total hip. Women who were switched from DEN to TER lost BMD at the distal radius, and showed losses of BMD in the femoral neck and total hip for the first 12 months, after which some gain in BMD occurred.

Ultimately, the greatest improvements in BMD were seen in women who were assigned initially to DEN + TER and then switched to DEN monotherapy. Hopefully, we will see similar trials in the future to guide us in switching between bisphosphonates and alternative agents such as denosumab.

ACE Inhibitors vs ARBs for Hypertension

SOURCE: Kaplan NM. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for hypertension: Are they equivalent? J Am Soc Hypertens 2015;9:582-583.

Recommendations from the panel assigned to develop Eighth Joint National Committee hypertension guidelines indicate that angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) (as well as thiazide-type diuretics and calcium channel blockers) are all appropriate initial therapies for hypertension in the general non-black population. For persons with chronic kidney disease and hypertension, this same document suggests ACE inhibitors or ARBs, without distinction. But should we consider ACE inhibitors and ARBs essentially interchangeable? An editorial review of this issue in the Journal of the American Society of Hypertension suggests otherwise, preferring ACE inhibitors over ARBs both in the general population and persons with diabetes.

The endorsement for ACE inhibitors over ARBs by this editorialist does not stem from a large randomized trial comparing the two. Rather, meta-analyses of a large number of hypertension trials has shown that whereas ACE inhibitors consistently reduced cardiovascular mortality, including myocardial infarction, ARBs do not demonstrate the same convincing risk reduction, especially for myocardial infarction. Since a large randomized trial comparing ACE inhibitors to ARBs is highly unlikely in the near future, if at all, this data review would support using ACE inhibitors preferentially over ARBs in most patients with hypertension.

Uric Acid as a Predictor of Hypertension

SOURCE: Leiba A, et al. Uric acid levels within the normal range predict increased risk of hypertension: A cohort study. J Am Soc Hypertens 2015;9;600-609.

Currently accepted laboratory standards indicate that the upper limit of “normal” for uric acid levels is 7 mg/dL in men and 6 mg/dL in women. Uric acid has been recognized as a cardiovascular risk factor for more than 3 decades, thanks to data from the Framingham study. Nonetheless, whether uric acid causes — or is simply associated with — adverse cardiovascular outcomes is uncertain. Additionally, even if the association of uric acid with cardiovascular disease is determined to be causal, it will remain necessary to definitively prove that reductions in uric acid improve outcomes (without undue risk).

Using analysis from the largest HMO in Israel, healthy adults aged 40-70 years (n = 118,920) had baseline uric acid levels obtained in 2002, and were subsequently followed for 10 years. During this interval, almost one-quarter of these had a new diagnosis of hypertension recorded. The risk of hypertension in women and men began to increase well within the “normal” range. Compared to a uric acid of 2-3 mg/dL, even patients with uric acid of 3-4 mg/dL were 15% more likely to become hypertensive; higher “normal” uric acid (5-6 mg/dL) was associated with a 66% increased incidence of hypertension. Results were similar for both women and men. The authors suggested that our currently defined levels of “normal” for uric acid may have to be reconsidered.