Objectives

Little is known about tissue changes underlying bone marrow lesions (BMLs) in non-weight-bearing joints with osteoarthritis (OA). Our aim was to characterize BMLs in OA of the hand using dynamic histomorphometry. We therefore quantified bone turnover and angiogenesis in subchondral bone at the base of the thumb, and compared the findings with control bone from hip OA.

Fracture prevention has so far been studied in patients included on the basis of low bone density, and not after a fracture. In this study the inclusion criteria was a new hip fracture irrespective of bone density. An international, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial (HORIZON-RFT) studied whether the bisphosphonate, zoledronic acid (ZOL) 5 mg, reduced subsequent clinical fractures in men and women ≥50 yrs after a hip fracture.

Methods: Patients with hip fracture were included. They received daily vitamin D3 and calcium supplements. Of 2127 randomized, 2111 were treated with once-yearly IV infusions of ZOL 5 mg (n=1054) or placebo (PBO; n=1057) and followed until 211 experienced new clinical fractures (the primary efficacy endpoint).

Results: Baseline characteristics were similar. Median age was 76 yrs (range, 50–98); 76% were women. Clinical fractures occurred in 92 ZOL and 139 PBO patients. 2-year cumulative event rates were 8.59% and 13.88%, respectively (Kaplan-Meier); relative risk reduction was 35% (HR=0.65; 95% CI: 0.50–0.84; P=.0012). ZOL reduced risk for clinical vertebral and nonvertebral fractures vs. PBO by 46% (HR=0.54; 95% CI: 0.32–0.92; P=.0210) and 27% (HR=0.73; 95% CI: 0.55–0.98; P=.0338), respectively. ZOL reduced risk of hip fractures by 30% vs. PBO (HR=0.70; 95% CI: 0.41–1.19; P=NS). AEs and SAEs were comparable between groups. There were no significant differences in cardiovascular parameters or long-term renal function. No cases of ONJ were reported. Death occurred in 9.58% of ZOL patients vs 13.34% PBO, a 28% lower mortality risk (HR=0.72; 95% CI: 0.56–0.93, P=.0117).

Conclusions: Subjects with a new hip fracture treated with annual IV ZOL infusions experienced significantly fewer clinical fractures vs. placebo. ZOL was well tolerated with a favorable safety profile. This is the first trial demonstrating a mortality benefit for an antiresorptive agent.