Effect of ONO-5334 on bone mineral density and biochemical markers of bone turnover in postmenopausal osteoporosis: 2-year results from the OCEAN study

Journal of Bone and Mineral Research, 07/26/2013

The aim of this study was to examine the efficacy and safety of 24months treatment with ONO–5334 and to assess the effect of treatment cessation over 2months. Cathepsin K inhibition with ONO–5334 resulted in decreases in most resorption markers over 2 years, but did not decrease most bone formation markers. This was associated with an increase in BMD; the effect on biochemical markers was rapidly reversible on treatment cessation.

Methods

  • The authors studied 197 postmenopausal women with osteoporosis or osteopenia with one fragility fracture.
  • Patients were randomised to ONO-5334 50 mg twice daily, 100 mg or 300 mg once daily, alendronate 70 mg once weekly (positive control) or placebo for 24 months.
  • After 24 months, all ONO-5334 doses were associated with increased bone mineral density (BMD) for lumbar spine, total hip and femoral neck (p < 0.001).

Results

  • ONO-5334 300 mg significantly suppressed the bone-resorption markers urinary (u) NTX and serum and uCTX-I throughout 24 months of treatment, and to a similar extent as alendronate; other resorption marker levels remained similar to placebo (fDPD for ONO-5334 300 mg qd) or were increased (ICTP, TRAP5b, all ONO-5334 doses).
  • Levels of B-ALP and PINP were suppressed in all groups (including placebo) for approximately 6 months, but then increased for ONO-5334 to close to baseline levels by 12–24 months.
  • On treatment cessation, there were increases above baseline in uCTX-I, uNTX and TRAP5b, and decreases in ICTP and fDPD.
  • There were no clinically relevant safety concerns.

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