DENVER (FRONTLINE MEDICAL NEWS) – A treatment regimen for postmenopausal women with osteoporosis that started with teriparatide (TPTD) for 2 years and switched to denosumab (DMAB) improved their spine trabecular microarchitecture – a predictor of fracture risk independent of areal bone mineral density – in a new analysis of the DATA trial and its extension study, DATA-Switch.
On the other hand, the converse strategy of switching from denosumab to teriparatide resulted in a temporary decline in bone mineral density. “The observed transient decrease in bone density corresponds to extremely elevated bone formation and resorptions markers, suggesting that high bone turnover is a cause of the transient loss,” Joy Tsai, MD , an instructor in medicine at Massachusetts General Hospital, Boston, said in an interview at a poster session of the annual meeting of the American Society for Bone and Mineral Research.
The conclusions are drawn from the 2-year DATA study ( J Clin Endocrinol Metab. 2014;99;1694-1700 ), which also showed that the combination of teriparatide and denosumab outperformed either drug alone, and the cumulative 4-year outcomes from its extension study, DATA-Switch ( Lancet. 2015 Dec 19. 386:1147-55 ).
“Our take-home is that for patients who are at extremely high risk of fracture, combination strategy is a treatment strategy to be considered,” said Dr. Tsai, who presented the results of the study at the meeting.
The findings also reinforce the general strategy of treating with anabolic therapy followed by an antiresorptive agent, rather than the other way around.
Specifically, “we would caution against the use of teriparatide immediately following denosumab because of this transient decrease in bone density that correlates with high bone turnover,” Dr. Tsai said.
The DATA and DATA-Switch studies randomized 94 postmenopausal women with osteoporosis to 2 years of TPTD (20 mcg/day), DMAB (60 mg every 6 months), or both drugs for 2 years. In DATA-Switch, women who received TPTD in the first 2 years were switched to DMAB, and those receiving DMAB were switched to TPTD. Women in the combination group were switched to DMAB only.
The researchers used dual-energy x-ray absorptiometry (DXA) spine scans to assess spine trabecular microarchitecture by calculating trabecular bone score (TBS) at 0, 12, 24, 30, 36, and 48 months.
After 2 years, TPTD alone was associated with a 2.7% increase in TBS over baseline (P = .009), while DMAB alone was associated with a 1.8% increase (P = .118 vs. baseline). Combination treatment led to a 4.5% increase (P = .017 vs. baseline).
In the 6 months after the treatment switch at year 2, the researchers noted increases in TBS in the combination-to-DMAB group (2.1%) and the TPTD-to-DMAB group (2.0%), but the DMAB-to-TPTD group experienced a decrease of 1.1% over months 24-30 (P less than .05 compared with other groups).
The decrease in TBS was temporary: At 48 months, all groups had an overall increase in TBS (TPTD-to-DMAB group, 5.1%; DMAB-to-TPTD group, 3.6%; combination-to-DMAB group, 6.1%). There were no significant differences between the groups.
From baseline to month 48, the percentage of patients considered to be at high risk of fracture based on TBS score (1.23 or less) dropped from 24% to 8% in the TPTD-to-DMAB group, from 18% to 14% in the DMAB-to-TPTD group, and from 39% to 11% in the combination-to-DMAB group.
“Ultimately, at the 4-year mark all three groups increased trabecular bone scores, so it also supports our rationale to consider the use of these treatment strategies, specifically the ones when you’re switching to or continuing denosumab,” Dr. Tsai said.
Amgen and Eli Lilly funded the study. Dr. Tsai reported having no financial disclosures.