Osteoporosis Medications Denosumab and Alendronate Have No Significant Effect on Vascular Calcification: SALTIRE2

"Osteoporosis treatments, including alendronic acid (Fosamax) and denosumab (Prolia), did not help with coronary or aortic calcification," the researchers reported. The findings indicate that these drugs neither promote nor inhibit vascular calcification.

Denosumab, a monoclonal antibody that inhibits bone resorption by targeting RANKL, and alendronate, a bisphosphonate that reduces bone loss by inhibiting osteoclast activity, have been the cornerstone of osteoporosis management for years. While osteoporosis is associated with increased vascular calcification, the impact of osteoporosis treatments on this condition remains uncertain. To fill this knowledge gap, Jolien Geers, BHF Centre for Cardiovascular Science University of Edinburgh Edinburgh UK, and colleagues aimed to investigate whether coronary or aortic calcification is influenced by denosumab and alendronic acid treatment.

For this purpose, the researchers conducted the double-blind randomized controlled SALTIRE2 trial (Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis). In this study, patients with aortic stenosis were randomly assigned in a 2:1:2:1 ratio to receive denosumab, placebo injection, alendronic acid, or placebo capsule.

The participants underwent serial imaging using computed tomography and 18F-sodium fluoride positron emission tomography to evaluate vascular calcium burden and calcification activity, respectively. The prespecified secondary analyses focused on changes over 24 months in coronary calcium score and 12 months in thoracic aorta calcium score, as well as in the 18F-sodium fluoride activity in both coronary and aortic regions.

The following were the key findings of the study:

• One hundred fifty patients with aortic stenosis (72±8 years; 21% female) were randomized to denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25).
• There were no differences in change in coronary calcium scores between placebo (16 Agatston units) and either denosumab (94 Agatston units) or alendronic acid (34).
• There were no differences in change in thoracic aorta calcium scores between placebo (132 Agatston units) and either denosumab (118) or alendronic acid (116 Agatston units).
• There were no differences in changes in coronary or aortic 18F‐sodium fluoride activity between treatment groups.

The findings revealed that neither alendronic acid nor denosumab affected the activity or progression of coronary or aortic calcification.

"The results suggest that osteoporosis treatments do not significantly impact vascular calcification associated with atherosclerosis," the researchers concluded.

Reference:

Geers J, Bing R, Pawade TA, Doris MK, Daghem M, Fletcher AJ, White AC, Forsyth L, Evans E, Kwieciński J, Williams MC, van Beek EJR, Kwak S, Peeters FECM, Tzolos E, Slomka PJ, Lucatelli C, Ralston SH, Prendergast B, Newby DE, Dweck MR. Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial. J Am Heart Assoc. 2024 Sep 9:e032571. doi: 10.1161/JAHA.123.032571. Epub ahead of print. PMID: 39248270.