Bisphosphonate use reduced BMD loss after halting denosumab in postmenopausal women

Bisphosphonate use before denosumab discontinuation was associated with less bone mineral density loss among postmenopausal women, according to findings presented at the EULAR Annual Congress.

“Our study suggests that being younger, having higher bone turnover markers and not having received zoledronate before denosumab introduction increase the risk of bone mineral density loss following discontinuation of denosumab,” Bérengère Aubry-Rozier, MD, of the rheumatology unit at Lausanne University Hospital in Lausanne, Switzerland, said in a press release.

Aubry-Rozier and colleagues followed 170 postmenopausal women to determine factors associated with BMD loss at 1 year after denosumab discontinuation. They defined BMD loss as a significant lumbar spine loss of more than 3.96%. The researchers found that 71 postmenopausal women ceased denosumab therapy after 7.7 ± 2.2 injections.

The cohort had a BMI of 23.8 ± 4.5, with 0.96 fractures per patient. Previous exposure to corticoids was reported in 8.45%, while 22.54% had exposure to anti-aromatase therapies. At just over 17 months following the last denosumab injection, they observed that 30 patients were had BMD loss — the “losers” group —and 41 were described as stable.

When denosumab was initiated, patients in the losers group were younger, 61.4 ± 7.3 years vs. 65.5 ± 8.2 years (P = .034). Losers also had higher levels of the bone turnover marker sCTX: 644.7 ng/ml vs. 474.1 ng/ml (P = .005).

Results showed no differences between the two groups in the rate of bisphosphonate use less than 2 years before denosumab therapy, according to the findings. However, no patient in the loser group had received zoledronate, while 12% of those in the stable group had received this drug (P = .047).

Patient characteristics prior to denosumab initiation were comparable between the loser and stable groups, as were the number of denosumab injections, bone turnover markers and BMD values

The researchers measured the first bone turnover markers at 7.5 months after the final denosumab injection and before initiation of bisphosphonate therapy. At that point, no differences were reported in sCTX between the losers (592 ng/ml) and stable patients (379 ng/ml; P = .06).

When denosumab was discontinued, 59% patients received zoledronate, 24% received alendronate, 3% of patients were treated with other medications, and 14% went untreated (P = .39 between groups).

Bone turnover markers as measured by sCTX were higher in the losers than stable patients at just over 1 year following bisphosphonate treatment (537 ng/ml vs. 336 ng/ml; P = .009).

“Our results support the use of denosumab after a bisphosphonate to reduce the bone mineral density loss at its discontinuation, and close monitoring of sCTX to maintain levels below the upper limit of the normal range for premenopausal women,” Aubry-Rozier said. —by Rob Volansky

Reference:
Aubry-Rozier B, et al. OP0085. Presented at: EULAR Annual Congress; June 12-15; Madrid, Spain.

Disclosure: Aubry-Rozier reports being on the speakers’ bureau of Amgen, Lilly, Novartis, and Pfizer.