Effect of Bone Resorption Inhibitors on Serum Cholesterol Level and Fracture Risk in Osteoporosis: Randomized Comparative Study Between Minodronic Acid and Raloxifene

Calcif Tissue Int. 2023 Apr;112(4):430-439. doi: 10.1007/s00223-023-01060-9. Epub 2023 Jan 28.


The positive link between osteoporosis and hypercholesterolemia has been documented, and bone resorption inhibitors, such as nitrogen-containing bisphosphonates (N-BP) and selective estrogen receptor modulators (SERMs), are known to reduce serum cholesterol levels. However, the relationship between the baseline cholesterol level and incident fracture rate under the treatment using the bone resorption inhibitors has not been documented. We investigated the relation between vertebral fracture incident and the baseline cholesterol levels and cholesterol-lowering effect of N-BP and SERM in osteoporosis through a prospective randomized open-label study design. Patients with osteoporosis (n = 3986) were allocated into two groups based on the drug used for treatment: minodronic acid (MIN) (n = 1624) as an N-BP and raloxifene (RLX) as an SERM (n = 1623). Serum levels of cholesterol and incidence of vertebral fracture were monitored for 2 years. The vertebral fracture rates between the two groups were compared using the pre-specified stratification factors. The patients receiving MIN with baseline low-density lipoprotein (LDL)-cholesterol level of ≥ 140 mg/dL, high-density lipoprotein cholesterol level < 40 mg/dL, age group of ≥ 75 years, and T score of BMD ≥ -3 SD had significantly lower vertebral fracture rates than those receiving RLX (incidence rate ratios (IRR) 0.45 [95% confidence interval (CI) 0.30 0.75, p = 0.001], 0.25 [95% CI 0.09 0.65, p = 0.005], 0.71 [95% CI 0.56 0.91, p = 0.006], 0.47 [95% CI 0.30 0.75, p = 0.0012], respectively). The cholesterol-lowering effect was stronger in the RLX group than in the MIN group, regardless of prior statin use. These results indicated that MIN treatment was more effective in reducing fracture risk in patients with higher LDL cholesterol levels, although its cholesterol-lowering ability was lesser than the RLX treatment.Trial registration University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR), No. UMIN000005433; date: April 13, 2011.

Keywords: Cholesterol; Fractures; Nitrogen-containing bisphosphonates; Osteoporosis; Selective estrogen receptor modulators.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Bone Density
  • Bone Density Conservation Agents* / pharmacology
  • Bone Density Conservation Agents* / therapeutic use
  • Cholesterol
  • Female
  • Fractures, Bone* / etiology
  • Humans
  • Osteoporosis* / complications
  • Osteoporosis* / drug therapy
  • Osteoporosis, Postmenopausal* / drug therapy
  • Prospective Studies
  • Raloxifene Hydrochloride / pharmacology
  • Raloxifene Hydrochloride / therapeutic use
  • Selective Estrogen Receptor Modulators / pharmacology
  • Selective Estrogen Receptor Modulators / therapeutic use
  • Spinal Fractures* / complications


  • Raloxifene Hydrochloride
  • Bone Density Conservation Agents
  • Selective Estrogen Receptor Modulators
  • Cholesterol