Abaloparatide improves bone strength among women with osteoporosis
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Women with osteoporosis receiving abaloparatide for 18 months followed by alendronate for 2 years had greater improvements in trabecular bone score than those receiving placebo, according to study findings.
“Abaloparatide (Tymlos, Radius Health) improves not only bone density, but also the microarchitecture of bone tissue, an important manifestation of bone quality,” Felicia Cosman, MD, professor of medicine in the division of endocrinology at Columbia University College of Physicians and Surgeons, told Healio. “Both bone mass and bone quality are important determinants of fracture risk, and improvements are related to superior fracture risk reduction.”
Cosman and colleagues conducted a retrospective analysis of data on 911 women who completed the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) and the ACTIVExtend trial and had trabecular bone score calculated at baseline and the end of both trials. Of the cohort included in the analysis, 457 were randomly assigned to once-daily 80 µg abaloparatide and 454 received placebo for 18 months. All participants received 70 mg alendronate once weekly for 24 months during ACTIVExtend. DXA scans were performed at baseline, 18 months and 43 months to calculate trabecular bone score, with values correcting for soft tissue based on abdominal tissue thickness. Participants were considered to have degraded bone microarchitecture with a trabecular bone score of less than 1.027, and a score between 1.027 and 1.074 was defined as moderately degraded microarchitecture.
The findings were published in The Journal of Bone and Mineral Research.
At baseline, 40% of women in the abaloparatide group and 43% receiving placebo had degraded bone microarchitecture. Trabecular bone score improved by 2.4% at 6 months and by 4% at 18 months in the abaloparatide group, with no significant change observed in placebo. During ACTIVExtend, trabecular bone score increased 0.4% in the abaloparatide group and 2.1% in the placebo group. The cumulative increase in trabecular bone score from baseline to 43 months was 4.4% in women receiving abaloparatide followed by alendronate vs. 1.7% in those receiving placebo followed by alendronate (P < .001).
The proportion of women with degraded bone microarchitecture in the abaloparatide group dropped from 40% at baseline to 24% at 18 months, whereas no change was observed in the placebo group. At 43 months, 21% of the abaloparatide group and 37% of the placebo group had degraded bone microarchitecture.
“The mean increase in trabecular bone score in this study with abaloparatide followed by alendronate is similar to the increase seen with another potent anabolic/antiresorptive sequence, romosozumab-aqqg (Evenity, Amgen) followed by alendronate,” Cosman said. “We also observed a 50% decline in the percentage of patients who had degraded trabecular bone score, also highlighting the improvement in cancellous bone microarchitecture and quality.”
At 43 months, 0.9% of the abaloparatide group and 5.1% of the placebo group had a vertebral fracture. Most of the fractures were sustained by women whose trabecular bone score change was less than the least significant change, which is the extent of change required for clinical significance.
“The data help support the observations from bone biopsy studies of teriparatide (Forteo, Eli Lilly; Bonsity, Alvogen) action performed years ago,” Cosman said. “In those studies, we saw increased trabecular number and connectivity in cancellous bone tissue of the iliac crest in patients on teriparatide. Now we have noninvasive evidence of this phenomenon occurring with abaloparatide in the clinically relevant site — the lumbar spine. The underlying rationale for the superior benefit of an anabolic treatment, such as abaloparatide compared with antiresorptive therapy, is that it improves both the microscopic structure of bone tissue as well as the mass. The trabecular bone score improvement with abaloparatide provides this evidence using a noninvasive technique.”
For more information:
Felicia Cosman, MD, can be reached at felcosman@gmail.com.
Perspective
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Bone densitometry is a useful tool in identifying risk for fracture and response to therapy, but as we know, it is very limited and does not account for bone quality. The majority of fragility fractures occur in people with osteopenia on bone densitometry, and percent changes can be low with first-line antiresorptive therapy.
This study highlights the impact on trabecular bone with abaloparatide, which was expected based on the anabolic action of this drug. The trabecular bone score change was similar to changes seen with teriparatide. Romosozumab’s impact on trabecular bone score was described in 10 patients and was just over 3% compared with 4% or more for parathyroid hormone analogs. There was not sufficient vertebral fracture data to show that trabecular bone score change was clearly linked with fracture reduction. One arm of this trial in the first 18 months was with teriparatide with approximately 450 patients. These patients did not go on to receive alendronate for 24 months in ACTIVE Extend and were not included in the analysis.
It would be interesting to see if data from this arm improves the statistical power of the study in terms of trabecular bone score prediction of fracture risk. In a prior study with teriparatide, trabecular bone score and bone density did not necessarily correlate well. It would be interesting to know if bone mineral density and trabecular bone score are clearly correlated for abaloparatide.
Abaloparatide is a potent anabolic medication, and recently received an indication for osteoporotic men at high risk for fracture in addition to postmenopausal women. Trabecular bone score change would be an exciting additional tool to help determine response to therapy.
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