Background/Purpose: Osteoporosis (OP) and osteoarthritis (OA) are often comorbid conditions in the elderly, with prevalence of OP in patients with OA reported as high as 30%. Previous studies have found significantly higher baseline BMD in OA patients than their non-OA counterparts, despite an increased risk for fracture, potentially contributing to delayed diagnosis and treatment in this population. In the ACTIVE phase 3 study of postmenopausal OP women, 18 months (M) of abaloparatide (ABL) treatment significantly increased bone mineral density (BMD) and reduced the risk of new vertebral, nonvertebral, clinical, and major OP fractures vs placebo (PBO) (NCT01343004). Women receiving ABL or PBO in ACTIVE were offered enrollment in the ACTIVExtend extension study in which both groups received 24M open-label alendronate (ALN) 70 mg weekly for a total of 43M (18M ABL or PBO, 1M for reconsent, and 24M ALN) (NCT01657162). The objective of this post hoc analysis was to evaluate efficacy and safety of ABL followed by ALN (ABL/ALN) vs PBO/ALN in the subgroup of patients with OA.

Methods: ACTIVExtend enrolled postmenopausal women with OP between the ages of 50 and 85; 558 were from the original ABL group and 581 from the PBO group of the ACTIVE study. Patients with the following terms in their medical history were included: “ongoing osteoarthritis” (including spine, knee, hand, foot, shoulder, and other sites), “spinal osteoarthritis”, “nodal/ hand osteoarthritis”, or “intervertebral disc degeneration”. New vertebral fracture incidence was evaluated using the modified intent-to-treat (mITT) population, other efficacy endpoints were evaluated using the ITT population. The percent mean changes in BMD from baseline to 43 months were calculated for the total hip (TH), femoral neck (FN), and lumbar spine (LS).

Results: A total of 395 ACTIVExtend patients with ongoing OA were identified (ABL/ALN, 190; PBO/ALN, 205). Most common sites of OA were at the knee (39.2%), and spine (38.5%). At baseline, 78 (19.7%) had a prevalent VF, 94 (23.8%) reported ≥1 prior NVF within the last 5 years, and 175 (44.3%) had no prior fractures. At 43M, 1.1% (2/186) ABL/ALN and 7.0% (14/201) PBO/ALN patients experienced ≥ 1 new vertebral fracture (P=0.004). Kaplan-Meier estimated cumulative incidence for other fracture endpoints was similar across treatment groups. Mean percent change in BMD were all significantly greater with ABL/ALN vs PBO/ALN at all timepoints assessed (P < 0.001). At 43M, BMD mean percent change from baseline was 6.0% ABL/ALN vs 2.3% PBO/ALN at the total hip, 4.9% ABL/ALN vs 1.4% PBO/ALN femoral neck, and 14.3% ABL/ALN vs 6.7% PBO/ALN lumbar spine. Most common TEAEs overall were upper respiratory tract infection (9.0% vs 8.3%), arthralgia (7.9% vs 8.8%), worsening osteoarthritis (8.5% vs 6.4%), and back pain (7.9% vs 4.4%), for ABL/ALN vs PBO/ALN arms, respectively.

Conclusion: Improvements in vertebral fracture risk as well as significant gains in BMD were maintained through 43M with ABL/ALN vs PBO/ALN. This post hoc analysis suggests that ABL/ALN was effective in a subgroup of patients with OP and OA, with no new safety signals identified.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/abaloparatide-followed-by-alendronate-on-bone-mineral-density-and-fracture-incidence-in-postmenopausal-women-with-osteoporosis-and-osteoarthritis/