Amlodipine Bone Health and Density Impact: What the Evidence Actually Shows

What the Norvasc label says about calcium and bone

The label describes amlodipine as a dihydropyridine calcium antagonist that inhibits calcium influx across cell membranes, with a greater effect on vascular smooth muscle than on cardiac muscle, and states that serum calcium concentration is not affected [1]. Hypertension, chronic stable angina, vasospastic angina and selected coronary artery disease are the labeled uses; osteoporosis is not one of them [1].

Among events reported in under 1% but over 0.1% of patients, where the label says a causal relationship is uncertain, it lists arthralgia, arthrosis, muscle cramps and myalgia [1].

What the fracture data show

The largest relevant human dataset is a population-based case-control study built from nationwide registers. It included 124,655 people who sustained a fracture in 2000 and 373,962 age- and sex-matched controls, with drug use over the previous five years treated as the exposure [2].

After adjustment for potential confounders, calcium-channel blocker use was associated with 6% lower odds of any fracture (OR 0.94, 95% CI 0.91-0.96) [2]. Hip fracture risk was reduced by 7% to 14% in users of the three drug groups studied (beta-blockers, ACE inhibitors and calcium-channel blockers) [2].

A sub-analysis found a larger risk reduction with non-dihydropyridine calcium-channel blockers than with dihydropyridines [2]. Amlodipine is a dihydropyridine [1].

This is an observational case-control design, so the finding is an association rather than a demonstrated cause-and-effect relationship. The authors adjusted for socioeconomic and health-related confounders, but the design cannot show that the drug itself produced the difference [2].

How large is the class-level result?

The adjusted odds ratios in this study sit close to 1.0: 0.94 for any fracture with calcium-channel blockers, against 0.91 for beta-blockers and 0.93 for ACE inhibitors [2]. The authors described the reduction as small [2]. No major differences appeared between men and women, or between people younger and older than 70 [2].

Label side effects

The Norvasc label reports dose-related edema: 1.8% at 2.5 mg, 3.0% at 5 mg and 10.8% at 10 mg, versus 0.6% with placebo [1]. Dizziness was 1.1% at 2.5 mg, 3.4% at 5 mg and 3.4% at 10 mg, versus 1.5% with placebo [1]. Edema was more frequent in women (14.6% versus 5.1% on placebo) than in men (5.6% versus 1.4%) [1]. The label data do not show whether these effects changed fall or fracture risk.

The label also warns that symptomatic hypotension is possible, particularly in patients with severe aortic stenosis, though acute hypotension is unlikely because of the gradual onset of action [1].

Is amlodipine an osteoporosis treatment?

No. Amlodipine is not a labeled treatment for osteoporosis [1]. Its labeled uses are blood pressure lowering, angina, and reducing the risk of angina hospitalization and coronary revascularization in selected patients with documented coronary artery disease [1].