Abstract
PurposeThe occurrence of multiple vertebral fractures was reported after denosumab discontinuation. The use of bisphosphonates following denosumab has been suggested to prevent this bone loss. The aim of our observational trial was to evaluate the ability of risedronate to prevent the bone loss related to denosumab discontinuation in post-menopausal osteoporosis. MethodsEighteen female patients, aged 69.8 years (56–79), were followed. All patients were prescribed 35 mg of risedronate per week for 3 months, starting when the next denosumab injection would have been administered. We measured BMD at denosumab initiation (T0), denosumab withdrawal (T1), and nine months after the discontinuation of risedronate (1 year post-denosumab: T2). Results1 year after denosumab discontinuation, the mean bone loss at the spine was – 4.6 ± 5.2% for the total population, −0.3 ± 2.3% in patients with prior exposure to bisphosphonates, −6.3 ± 5.7% in patients with prior exposure to teriparatide, and − 7.6 ± 3.5% in naïve patients. Spine BMD loss after the risedronate bridging therapy (T2 vs. T1) was significantly lower in patients who experienced prior exposure to bisphosphonates, when compared to naïve patients (p = .0190) and to patients with prior teriparatide exposure (p = .0176). 1 year after denosumab discontinuation, the mean densitometric loss at the hip was −1.8 ± 3.4% in the total cohort, −0.6 ± 1.8% in the patients previously treated with bisphosphonates, −1.5 ± 4.7% in the patients previously treated with teriparatide, and − 4.2 ± 0.6 in naïve patients. The mean densitometric loss during the off-denosumab period was lower in patients with previous bisphosphonate exposure than in naïve patients (p = .043) and in patients with previous exposure to teriparatide (p = .05). ConclusionsThree months of risedronate treatment does not prevent bone loss in patients who have not been treated with bisphosphonates before denosumab.
Highlights
Multiple vertebral fracture has recently been reported after denosumab discontinuation (Anastasilakis et al, 2017; Anastasilakis et al, 2019)
Spine bone mineral density (BMD) loss after the risedronate bridging therapy (T2 vs. T1) was significantly lower in patients who experienced prior exposure to bisphosphonates, when compared to naïve patients (p = .0190) and to patients with prior teriparatide exposure (p = .0176). 1 year after denosumab discontinuation, the mean densitometric loss at the hip was −1.8 ± 3.4% in the total cohort, −0.6 ± 1.8% in the patients previously treated with bisphosphonates, −1.5 ± 4.7% in the patients previously treated with teriparatide, and − 4.2 ± 0.6 in naïve patients
In our Rheumatology Center, we proposed to 18 women, treated for at least 2 years with denosumab, who met the aforementioned criteria for treatment discontinuation (N = 16) or who presented side effects to this treatment (N = 2: One interruption was due to cataract, and one was due to requirements for dental implants) to switch from dmab to risedronate
Summary
Multiple vertebral fracture has recently been reported after denosumab discontinuation (Anastasilakis et al, 2017; Anastasilakis et al, 2019). The off-treatment extension studies with this drug showed a significant rebound in bone turnover markers, exceeding the initial levels for 48 months (Bone et al, 2011a, 2011b) This intense bone turnover was paralleled with a loss in bone mineral density (BMD) from the first year following denosumab discontinuation, both at spine and hip sites (Popp et al, 2018). The work of the European Calcified Tissue Society (ECTS) suggested a post-denosumab (dmab) bisphosphonate therapy to prevent/reduce rebound in bone turnover (Tsourdi et al, 2017). The aim of our study was to evaluate the ability of a 3-month risedronate bridging therapy to reduce BMD loss after denosumab discontinuation
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