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

  • 2025-02-18
  • Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 40(5)
    • Carolyn J Crandall
    • Sharon Chou
    • Eunjung Kim
    • Dana Ratnarajah
    • Nancy R Cook
    • Allison Clar
    • Howard D Sesso
    • JoAnn E Manson
    • Meryl S LeBoff

Study Design

Type
Randomized Controlled Trial (RCT)
Population
21 442 COSMOS participants (12 666 females aged ≥65 yr and 8776 males aged ≥60 yr)
Methods
ancillary study to COSMOS; randomized in a 2 × 2 factorial design to cocoa extract + MVM, cocoa extract + MVM placebo, cocoa extract placebo + MVM, or double placebo; daily cocoa extract 500 mg/d flavanols and 80 mg/d (-)-epicatechin; daily MVM supplement Centrum Silver; intention-to-treat analyses using Cox proportional hazards models
Blinding
Double-blind
Duration
3.6 (3.2-4.2) yr
Funding
Mixed (industry + independent)
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.

Research Insights

  • Cocoa→Reduced Nonvertebral Fracture

    cocoa extract was not significantly associated with lower risk of ... nonvertebral fracture (aHR 1.05, 95% CI 0.96-1.14)

    Effect
    Neutral
    Effect size
    Small
    Dose
    500 mg/d flavanols and 80 mg/d (-)-epicatechin
  • Cocoa→Reduced Total Clinical Fracture

    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)

    Effect
    Neutral
    Effect size
    Small
    Dose
    500 mg/d flavanols and 80 mg/d (-)-epicatechin
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