Amorphous calcium carbonate supplementation and bone outcomes in rheumatoid arthritis: A prospective cohort study

Medicine (Baltimore). 2026 Mar 6;105(10):e47846. doi: 10.1097/MD.0000000000047846.

Abstract

Rheumatoid arthritis (RA) is associated with increased risks of osteoporosis and fracture. Amorphous calcium carbonate (ACC) may enhance osteogenic differentiation and increase bone mineral density (BMD). The effects of ACC supplementation on BMD and bone turnover markers (BTMs) in RA have not been explored. This study investigated the influence of ACC supplementation on BMD, BTMs, and the risk of osteoporotic fractures in RA patients. We enrolled 67 RA patients with osteopenia or osteoporosis. BMD was measured by dual-energy X-ray absorptiometry before and after 1 year of ACC supplementation, providing elemental calcium 800 mg/day combined with vitamin D3 400 IU/day. Serum levels of N-terminal propeptide of type I collagen and C-terminal cross-linking telopeptide were measured at baseline and every 3 months following ACC supplementation. The 10-year fracture probability was calculated using the Fracture Risk Assessment Tool (FRAX®), and RA activity was assessed using the 28-joint disease activity score. Multivariate regression analysis revealed that age and corticosteroid dosage ≥5 mg were significant risk factors for major osteoporotic fracture. The 28-joint disease activity scores were inversely correlated with BMD of the right femoral neck (r = -0.426, P < .001) and left femoral neck (r = -0.383, P < .005). After 12 months of ACC supplementation, bilateral femoral neck BMD increased significantly (from 0.61 to 0.63 g/cm2, both P < .001), accompanied by improvement in T-scores. Serum levels of N-terminal propeptide of type I collagen and C-terminal cross-linking telopeptide were significantly decreased (mean 53.42 vs 41.24 ng/mL, P < .001; 0.29 vs 0.25 ng/mL, P < .05, respectively). Twelve-month ACC supplementation increased bilateral femoral neck BMD and reduced BTM levels in RA patients, particularly in anti-citrullinated peptide antibody-positive patients.

Keywords: amorphous calcium carbonate; bone mineral density; bone turnover markers; osteoporosis; rheumatoid arthritis.

Publication types

  • Observational Study

MeSH terms

  • Absorptiometry, Photon
  • Adult
  • Aged
  • Arthritis, Rheumatoid* / complications
  • Arthritis, Rheumatoid* / drug therapy
  • Biomarkers / blood
  • Bone Density* / drug effects
  • Bone Diseases, Metabolic / drug therapy
  • Calcium Carbonate* / administration & dosage
  • Calcium Carbonate* / therapeutic use
  • Cholecalciferol / administration & dosage
  • Dietary Supplements*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoporosis* / drug therapy
  • Osteoporosis* / etiology
  • Osteoporotic Fractures / etiology
  • Osteoporotic Fractures / prevention & control
  • Peptides / blood
  • Prospective Studies

Substances

  • Calcium Carbonate
  • Biomarkers
  • Peptides
  • Cholecalciferol