Improvement of periarticular osteoporosis in postmenopausal women with rheumatoid arthritis by beta-alanyl-L-histidinato zinc: a pilot study

J Bone Miner Metab. 2000;18(6):335-8. doi: 10.1007/s007740070005.


The effect of zinc on bone metabolism in patients with rheumatoid arthritis (RA) is unknown. In the present pilot study, we investigated the effect of two antiulcer drugs, beta-alanyl-L-histidinato zinc (AHZ) and cimetidine, on bone metabolism in postmenopausal women with RA who had bilateral wrist pain. Eight patients were enrolled in a prospective, single-blind study consisting of 6-month cimetidine treatment (400 mg/day) followed by 6-month AHZ treatment (300 mg/day). Biochemical markers and bone mineral density (BMD) by dual energy X-ray absorptiometry were measured at baseline, 6 months, and 12 months. Three patients withdrew, and five patients (mean age 60: range 55-64 years) were analyzed. Their disease activity including wrist pain and dosages of prednisolone and disease-modifying antirheumatic drugs remained unchanged during the 12-month treatment. The AHZ treatment increased serum zinc (AHZ vs cimetidine, +48.0% vs +5.6%), and resulted in significant increases of serum bone-specific alkaline phosphatase (+93.5% vs -14.7%) and BMD of the bilateral ultradistal radius (+4.9% vs -5.6%). However, the AHZ treatment had no effect on BMD of the lumbar spine (-2.0% vs +1.5%) or the bilateral distal third of radius (-2.1% vs +0.2%). In the AHZ treatment, the percentage change in BMD of the unilateral ultradistal radius with more severe wrist pain was positively correlated with the percentage change in serum zinc (r = 0.97). These findings suggest for the first time that AHZ treatment improves periarticular osteoporosis, probably through an increase of bone formation, in postmenopausal women with RA. Randomized double-blind controlled trials are needed.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Anti-Ulcer Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism
  • Bone Density / drug effects*
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Carnosine / analogs & derivatives*
  • Carnosine / therapeutic use*
  • Cimetidine / therapeutic use
  • Female
  • Humans
  • Middle Aged
  • Organometallic Compounds / therapeutic use*
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / metabolism
  • Pilot Projects
  • Prospective Studies
  • Single-Blind Method
  • Zinc Compounds


  • Anti-Ulcer Agents
  • Organometallic Compounds
  • Zinc Compounds
  • polaprezinc
  • Cimetidine
  • Carnosine
  • Alkaline Phosphatase