Effects of Abaloparatide or Placebo on Bone Mineral Density in Acetabular Regions Corresponding to DeLee and Charnley Zones in Postmenopausal Women with Osteoporosis

Abstract

Purpose/Aims

To evaluate the effects of 6 and 18 mo of abaloparatide (ABL) compared with placebo (PBO) on bone mineral density (BMD) in the acetabular regions of postmenopausal women with osteoporosis (OP).

Rationale/Background

Acetabular bone loss, as may occur in OP, increases risk of acetabular fragility fractures and is associated with significant morbidity. In total hip arthroplasty (THA), low acetabular BMD adversely affects primary stability, osseointegration, and migration of acetabular cups. ABL is an osteoanabolic agent for the treatment of men and postmenopausal women with OP at high risk for fracture that increases BMD of the total hip, femoral neck, trochanter, and lumbar spine. Effects of ABL on acetabular BMD are unknown.

Methods

Hip DXA scans were obtained at baseline, 6, and 18 mo from a random subgroup of postmenopausal women (aged 49–86 y) from the phase 3 ACTIVE trial randomized to either ABL 80 µg/d or PBO (n=250/group).

Anatomical landmarks were identified in each DXA scan to virtually place a hemispherical shell model of an acetabular cup and define regions of interest corresponding to DeLee & Charnley zones 1 (R1), 2 (R2), and 3 (R3). BMD changes compared to baseline were calculated for each zone. Statistical P values were based on a mixed-effect repeated measure model adjusted for BMI, age, and baseline BMD, with covariates including DXA scanner type, treatment group, visit, and treatment/visit interaction. DXA scans were aligned via intensity-based registration onto a reference scan to depict local mean changes in BMD.

Results

BMD in all zones were similar at baseline in the ABL and PBO groups. BMD significantly increased in the ABL group at 6 and 18 mo compared with PBO (all P< 0.0001 vs PBO; Figure), with mean BMD increasing from baseline by 8.38% in R1, 7.25% in R2, and 9.73% in R3 at 18 months. BMD in the PBO group was relatively stable over time.

Implications

Treatment with ABL resulted in rapid and progressive increases in BMD of all 3 acetabular zones. Increasing acetabular BMD has the potential to improve acetabular strength, which may reduce risk of acetabular fragility fractures. With bone health optimization prior to THA, increased acetabular BMD via ABL may provide better primary stability and longevity of acetabular cups in postmenopausal women with OP.