Effects of cocoa extract supplementation and multivitamin/multimineral supplements on self-reported fractures in the Cocoa Supplement and Multivitamins Outcomes Study randomized clinical trial.

Osteoporosis is a major public health problem among older adults. Forty percent of older US adults take multivitamin/multimineral (MVM) supplementation. The effects of MVM supplementation on fractures are unclear. Preclinical and observational studies suggest that MVM and flavanols may have beneficial effects on bone. We conducted an ancillary study to Cocoa Supplement and Multivitamin Outcomes Study (COSMOS; NCT05232669) designed to investigate incident fracture and injurious falls in 21 442 COSMOS participants (12 666 females aged ≥65 yr and 8776 males aged ≥60 yr) randomized in a 2 × 2 factorial design to 1 of 4 intervention groups: cocoa extract + MVM, cocoa extract + MVM placebo, cocoa extract placebo + MVM, or double placebo. The daily cocoa extract supplement contained 500 mg/d flavanols and 80 mg/d (-)-epicatechin (Mars Edge); the daily MVM supplement was Centrum Silver (Haleon). The median (interquartile range) duration of the intervention was 3.6 (3.2-4.2) yr. Annually, participants self-reported incident fractures. In intention-to-treat analyses, we examined the effects of cocoa extract and MVM on the primary outcomes of total clinical fracture (hip, upper leg, forearm/wrist, pelvis, upper arm/shoulder, spine, knee, or other), hip fracture, and nonvertebral fracture, and secondary outcomes of clinical spine, forearm/wrist, major osteoporotic, and pelvic fracture using Cox proportional hazards models. During the intervention period, 2083 incident clinical fractures occurred. Compared with placebo, cocoa extract was not significantly associated with lower risk of incident clinical fracture (adjusted hazard ratio [aHR] 1.03, 95% CI 0.95-1.12) or nonvertebral fracture (aHR 1.05, 95% CI 0.96-1.14). MVM supplementation was not associated with lower risk of total clinical fracture (aHR 1.09, 95% CI 1.00-1.19), hip fracture (aHR 1.06, 95% CI 0.80-1.42), or nonvertebral fracture (aHR 1.10, 95% CI 1.00-1.20). These findings do not support the use of cocoa extract or MVM to decrease fracture risk in older individuals not selected for pre-existing osteoporosis.