In the Journals

T-score 'key indicator' of fracture risk after long-term denosumab treatment

Most postmenopausal women with osteoporosis achieved a T-score above the osteoporosis threshold after receiving 10 years of denosumab therapy, with the incidence of nonvertebral fractures decreasing as a function of bone mineral density, according to findings published in the Journal of Bone and Mineral Research.

Serge Ferrari

Recently approved osteoporosis therapies, either alone or in combination, have led to large and continued gains in BMD, further spurring interest in BMD as a target for osteoporosis treatment, Serge Ferrari, MD, a professor of medicine at the Geneva Faculty of Medicine and head of the clinical service and research laboratory of bone diseases at Geneva University Hospital, Switzerland, and colleagues wrote in the study background.

“For treatment-naive patients, specific T-score thresholds are used to diagnose osteopenia and osteoporosis, and BMD is a robust predictor of fracture risk,” Ferrari and colleagues wrote. “Conversely, only a few studies have examined the extent to which the risk of fracture depends on the BMD achieved during treatment.”

Researchers analyzed data from 1,343 postmenopausal women aged 60 to 90 years at baseline who received 10 years of treatment with denosumab therapy (Prolia, Amgen) as part of the FREEDOM trial (3 years) and the FREEDOM Extension trial (up to 7 years). DXA scans of the proximal femur were evaluated once per year from baseline through year 6 and again at years 8 and 10. Women reported the occurrence of clinical fractures at scheduled visits every 6 months. Researchers assessed the percentages of women who achieved a range of T-scores at the total hip or femoral neck during 10 years of treatment.

Within the cohort, 373 women (10.3%) sustained nonvertebral fractures during denosumab treatment, including 42 hip fractures (1.2%) and 155 wrist fractures (4.3%). Researchers found that the incidence of hip fractures was lower among women with at least one postbaseline total hip T-score of at least –1.5 vs. those without at least one postbaseline total hip T-score of at least –1.5 (0.5% vs. 2%; P < .0001), as was the incidence of nonvertebral fractures (9% vs. 12%; P < .0001).

Researchers observed that the incidence of nonvertebral fractures was lower with higher total hip T-score; however, the observed association plateaued at a T-score between –2 and –1.5 and was independent of age and prevalent vertebral fractures.

“Absolute fracture risk was higher in older women and women with previous fractures for any T-score level; however, the inverse relationship between T-score attained and fracture risk reduction was maintained regardless of age or prior nonvertebral fracture history,” the researchers wrote.

From baseline through 10 years, the percentages of women with total hip T-scores of at least –2.5, –2 or –1.5 increased from 75%, 53% and 31%, respectively, to 95%, 81% and 61%, respectively, after denosumab treatment. Reaching a specific T-score during denosumab treatment was dependent on the baseline T-score, with higher T-scores at baseline more likely to result in higher T-scores at each time point during the study, according to the researchers.

“The incidence of nonvertebral fractures decreased significantly as a function of the T-score achieved during therapy, and this relationship was consistent across important demographic variables, such as age and prior fracture history, indicating that the absolute BMD attained on treatment is a key indicator of fracture risk,” the researchers wrote.

The researchers noted that regular monitoring of BMD during therapy may be useful to determine when fracture risk has reached a minimal threshold and treatment could be suspended or consolidated.

“Our observations support the concept of a treat-to-target approach in osteoporosis,” the researchers wrote. – by Regina Schaffer

Disclosures: Amgen funded this study. Ferrari reports he has served as a consultant for and received travel expenses from Amgen. Please see the study for all other authors’ relevant financial disclosures.

Most postmenopausal women with osteoporosis achieved a T-score above the osteoporosis threshold after receiving 10 years of denosumab therapy, with the incidence of nonvertebral fractures decreasing as a function of bone mineral density, according to findings published in the Journal of Bone and Mineral Research.

Serge Ferrari

Recently approved osteoporosis therapies, either alone or in combination, have led to large and continued gains in BMD, further spurring interest in BMD as a target for osteoporosis treatment, Serge Ferrari, MD, a professor of medicine at the Geneva Faculty of Medicine and head of the clinical service and research laboratory of bone diseases at Geneva University Hospital, Switzerland, and colleagues wrote in the study background.

“For treatment-naive patients, specific T-score thresholds are used to diagnose osteopenia and osteoporosis, and BMD is a robust predictor of fracture risk,” Ferrari and colleagues wrote. “Conversely, only a few studies have examined the extent to which the risk of fracture depends on the BMD achieved during treatment.”

Researchers analyzed data from 1,343 postmenopausal women aged 60 to 90 years at baseline who received 10 years of treatment with denosumab therapy (Prolia, Amgen) as part of the FREEDOM trial (3 years) and the FREEDOM Extension trial (up to 7 years). DXA scans of the proximal femur were evaluated once per year from baseline through year 6 and again at years 8 and 10. Women reported the occurrence of clinical fractures at scheduled visits every 6 months. Researchers assessed the percentages of women who achieved a range of T-scores at the total hip or femoral neck during 10 years of treatment.

Within the cohort, 373 women (10.3%) sustained nonvertebral fractures during denosumab treatment, including 42 hip fractures (1.2%) and 155 wrist fractures (4.3%). Researchers found that the incidence of hip fractures was lower among women with at least one postbaseline total hip T-score of at least –1.5 vs. those without at least one postbaseline total hip T-score of at least –1.5 (0.5% vs. 2%; P < .0001), as was the incidence of nonvertebral fractures (9% vs. 12%; P < .0001).

Researchers observed that the incidence of nonvertebral fractures was lower with higher total hip T-score; however, the observed association plateaued at a T-score between –2 and –1.5 and was independent of age and prevalent vertebral fractures.

“Absolute fracture risk was higher in older women and women with previous fractures for any T-score level; however, the inverse relationship between T-score attained and fracture risk reduction was maintained regardless of age or prior nonvertebral fracture history,” the researchers wrote.

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From baseline through 10 years, the percentages of women with total hip T-scores of at least –2.5, –2 or –1.5 increased from 75%, 53% and 31%, respectively, to 95%, 81% and 61%, respectively, after denosumab treatment. Reaching a specific T-score during denosumab treatment was dependent on the baseline T-score, with higher T-scores at baseline more likely to result in higher T-scores at each time point during the study, according to the researchers.

“The incidence of nonvertebral fractures decreased significantly as a function of the T-score achieved during therapy, and this relationship was consistent across important demographic variables, such as age and prior fracture history, indicating that the absolute BMD attained on treatment is a key indicator of fracture risk,” the researchers wrote.

The researchers noted that regular monitoring of BMD during therapy may be useful to determine when fracture risk has reached a minimal threshold and treatment could be suspended or consolidated.

“Our observations support the concept of a treat-to-target approach in osteoporosis,” the researchers wrote. – by Regina Schaffer

Disclosures: Amgen funded this study. Ferrari reports he has served as a consultant for and received travel expenses from Amgen. Please see the study for all other authors’ relevant financial disclosures.