Odanacatib Increased Bone Density in Women With Osteoporosis

SEATTLE — Odanacatib, a selective oral inhibitor of cathepsin K, appears to help increase trabecular, cortical, and integral volumetric BMD (vBMD) at the spine and total hip (TH) in postmenopausal women with osteoporosis.

This experimental agent may also increase the estimated whole-bone strength at the spine and hip, according to study results presented at the American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting.

Previously released data showed that, in the phase 3 LOFT (Long-Term Odanacatib Fracture Trial), odanacatib significantly reduced fracture risk and led to gradual increases in BMD at the lumbar spine (LS) and TH compared with placebo. In this updated analysis, the researchers used quantitative computerized tomography (QCT) to measure improvements.

“Odanacatib is an oral inhibitor of cathepsin K that inhibits bone resorption through a mechanism that is distinct from bisphosphonates. Previous studies have shown that treatment with odanacatib increases areal BMD as measured by DXA and prevents fractures. The present study using QCT demonstrates that odanacatib increases trabecular, cortical, and integral volumetric BMD at the spine and hip and increases estimated whole-bone strength at the spine and hip,” said lead study investigator Bente Langdahl, PhD, DMSc, who is a professor and consultant in the department of endocrinology and internal medicine at the THG Aarhus University Hospital in Denmark.

These new data indicate that both cortical and trabecular compartments of bone improve upon treatment with odanacatib, according to Dr Langdahl, who presented the findings at the meeting. 

Incidence of adverse events and serious adverse events had been previously been presented. Major cardiovascular (CV) events overall were generally balanced, except that there were numerically more adjudicated strokes with odanacatib vs placebo. Final blinded adjudication of major CV events is ongoing, she noted.

In a substudy of LOFT, Dr Langdahl and colleagues evaluated the effects of odanacatib on vBMD of trabecular and cortical bone by QCT. They also estimated whole-bone strength using finite element analysis (FEA).

The cohort included 164 women aged at least 65 years without a baseline radiographic vertebral fracture and a TH or femoral neck (FN) BMD T-score between –2.5 and –4.0. The cohort also included women who had a prior vertebral fracture and a TH or FN T-score between –1.5 and –4.0.

All of the women were enrolled at 10 centers in Denmark and South Africa. The women were then randomly assigned to odanacatib 50 mg per week (n=78) or placebo (n= 86). All participants were also prescribed vitamin D3 and calcium.

The researchers analyzed the percentage of change from baseline in trabecular vBMD at the spine (primary) and cortical vBMD at the TH (secondary) at 24 months.  

Using QCT and FEA, they also analyzed trabecular, cortical, and integral parameters at the spine and hip, and estimated whole-bone strength.  

The researchers found that those patients treated with odanacatib had significantly increased trabecular, cortical, and integral vBMD at the spine (L1) and TH compared with baseline and placebo.

The study also demonstrated that those patients receiving odanacatib had increased whole-bone estimated strength at the L1 vertebra and proximal femur. Whole-bone estimated strength at the L1 vertebra and proximal femur remained stable or decreased in the placebo arm.

“Treatment of postmenopausal osteoporotic women with odanacatib consistently improves cortical and trabecular volumetric BMD which underscores the previously demonstrated fracture preventive effect of odanacatib at both the hip and spine,” Dr Langdahl told Endocrinology Advisor.

Reference

1. Langdahl B. Abstract 1056: Effect of Odanacatib on Bone Density and Estimated Bone Strength in Postmenopausal Women: a CT-Based Sub-study of the Phase 3 Long-Term Odanacatib Fracture Trial (LOFT). Presented at: American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting; Oct. 9-12, 2015; Seattle.   
2. McClung M. Abstract 1147: Odanacatib Anti-Fracture Efficacy and Safety in Postmenopausal Women with Osteoporosis. Results from the Phase III Long-Term Odanacatib Fracture Trial (LOFT). Presented at: American Society for Bone and Mineral Research (ASBMR) 2014 Annual Meeting; Sept. 12-15, 2014; Houston.
3. Papapoulos S. Abstract 1148: Safety and Tolerability of Odanacatib Therapy in Postmenopausal Women with Osteoporosis: Results from the Phase III Long-Term Odanacatib Fracture Trial (LOFT). Presented at: American Society for Bone and Mineral Research (ASBMR) 2014 Annual Meeting; Sept. 12-15, 2015; Houston.