Wrist fractures are the most common fracture of the upper extremity, and fractures of the distal radius account for approximately 18% of fractures in adults over 65 years of age [
1,
2]. Women with postmenopausal osteoporosis who have experienced a wrist fracture are ~ 50% more likely to experience functional decline and are at increased risk of subsequent nonwrist fractures [
3,
4].
Most fractures of the wrist occur at the ultradistal (UD) radius, which contains a high proportion of trabecular bone, so measurement of bone mineral density (BMD) at the UD radius may improve prediction of fracture compared with BMD measurement at the femoral neck alone [
5‐
8]. However, the 1/3 radius, a region that is composed predominantly of denser cortical bone, is the forearm site most commonly reported by dual-energy x-ray absorptiometry (DXA) [
5,
7,
8].
Abaloparatide (ABL) is a selective activator of the parathyroid hormone receptor type 1 (PTHR1) signaling pathway, which results in direct stimulation of bone formation, improvement in bone microarchitecture, and enhanced measures of bone strength [
9‐
11]. In the 18-month Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) phase 3 study, ABL significantly reduced the risk of vertebral, nonvertebral, and clinical fractures and increased BMD at the lumbar spine, total hip, and femoral neck compared with placebo (PBO) in postmenopausal women aged 49 to 86 years with osteoporosis [
12]. ABL also significantly reduced the risk of major osteoporotic site fractures (collectively defined as clinical spine, hip, upper arm, and wrist) compared with patients treated with teriparatide (TPTD) and PBO [
12]. In a prespecified subanalysis of ACTIVE, ABL significantly increased BMD at the UD radius vs PBO and TPTD, whereas BMD at the 1/3 radius declined in all three treatment groups [
13]. BMD effects were associated with a trend for numerically lower wrist fracture incidence for ABL (
n = 7/824 (Kaplan-Meier (KM) estimate, 1.0%)) compared with TPTD (
n = 17/818 (KM estimate, 2.3%),
P = 0.052) and PBO (
n = 15/821 (KM estimate, 2.2%),
P = 0.11) [
13].
Women receiving ABL or PBO in ACTIVE were offered enrollment in the ACTIVExtend extension study in which both groups received 24 months of open-label alendronate (ALN) 70 mg/week for a total of 43 months [
14]. In ACTIVExtend, patients treated with ABL in ACTIVE who switched to ALN for 24 months had greater sustained reduction in fracture risk and increased BMD compared with PBO followed by ALN [
14].
The objectives of this study, a prespecified subanalysis of ACTIVExtend, were to determine the efficacy of 18 months of ABL followed by 24 months of ALN (ABL/ALN) vs PBO followed by ALN (PBO/ALN) on BMD at the UD radius and 1/3 radius and to assess the incidence of wrist fractures.