Fracturas vertebrales múltiples tras la suspensión de tratamiento con denosumab: serie de diez casos

Fernández-Fernández, E.; Nuñez, Diego; Hernán, Gema Bonilla; Monjo, I.; Carazo, Sara; Pineda, Miguel Bernad; Criado, Alejandro; Acín, Pilar Aguado

doi:10.1016/j.reuma.2018.11.002

Cited by 6 publications

(2 citation statements)

References 11 publications

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“…(1) Cessation, of treatment, however, is followed by rapid reversal of its favorable skeletal effects, associated in a few patients with multiple vertebral fractures. (2)(3)(4)(5)(6)(7)(8)(9)(10) This is attributed to an increase in bone turnover above pretreatment values, a response described as "rebound phenomenon" probably due to upregulation of osteoclastogenesis. (2,3,11) To prevent this sequence of events, it is recommended that patients discontinuing Dmab therapy should be administered bisphosphonates.…”

Section: Introductionmentioning

confidence: 99%

Zoledronate for the Prevention of Bone Loss in Women Discontinuing Denosumab Treatment. A Prospective 2-Year Clinical Trial

Anastasilakis

Papapoulos

Polyzos

et al. 2019

Journal of Bone and Mineral Research

113

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Cessation of denosumab treatment is associated with increases in bone turnover above baseline values and rapid bone loss. We investigated the efficacy of zoledronate to prevent this bone loss in women with postmenopausal osteoporosis who were treated with denosumab (mean duration 2.2 years) and discontinued treatment after achieving osteopenia. Women were randomized to receive a single 5‐mg infusion of zoledronate (ZOL) (n = 27) or two additional 60‐mg injections of denosumab (Dmab) (n = 30). Both groups were followed for a total period of 24 months. At 24 months lumbar spine–bone mineral density (LS‐BMD) was not different from baseline in the ZOL group, but decreased in the Dmab group by (mean ± SD) 4.82% ± 0.7% (p < 0.001) from the 12‐month value; the difference in BMD changes between the two groups, the primary endpoint of the study, was statistically significant (p = 0.025). Results of femoral neck (FN)‐BMD changes were similar. ZOL infusion was followed by small but significant increases in serum procollagen type 1 N‐terminal propeptide (P1NP) and C‐terminal telopeptide of type 1 collagen (CTX) during the first year and stabilization thereafter. In the Dmab group, bone turnover marker values did not change during the first 12 months but increased significantly at 15 months and in the majority of women these remained elevated at 24 months. Neither baseline nor 12‐month bone turnover marker values were associated with BMD changes in either group of women. In the Dmab group, three patients sustained vertebral fractures (two patients multiple clinical, one patient morphometric) whereas one patient in the ZOL group sustained clinical vertebral fractures 12 months after the infusion. In conclusion, a single intravenous infusion of ZOL given 6 months after the last Dmab injection prevents bone loss for at least 2 years independently of the rate of bone turnover. Follow‐up is recommended, because in a few patients ZOL treatment might not have the expected effect at 2 years. © 2019 American Society for Bone and Mineral Research.

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Section: Introductionmentioning

confidence: 99%

Zoledronate for the Prevention of Bone Loss in Women Discontinuing Denosumab Treatment. A Prospective 2-Year Clinical Trial

Anastasilakis

Papapoulos

Polyzos

et al. 2019

Journal of Bone and Mineral Research

113

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“…Some warning signs need to be explored and are well known after treatment with denosumab. A major rebound effect after stopping denosumab can be responsible for rapid bone loss with vertebral crushes [1][2][3][4][5][6]. Some other manifestations have been described, such as hypercalcemia in both children [7][8][9][10][11][12][13] and adults [14], hyperparathyroidism [15], and vertebral osteonecrosis [16].…”

Section: Introductionmentioning

confidence: 99%

Long-term follow up after denosumab treatment for osteoporosis – rebound associated with hypercalcemia, parathyroid hyperplasia, severe bone mineral density loss, and multiple fractures: a case report

et al. 2020

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Background: The rebound effect after stopping treatment with denosumab may be associated with rapid loss of the gains in bone mineral density achieved with treatment, high levels of bone remodeling markers, the occurrence of vertebral fractures, and even hypercalcemia. Case presentation: A 64-year-old osteoporotic Caucasian woman suffered from a fracture of her second lumbar vertebra in 2004. From January 2005, she was treated with denosumab for 9 years, with good densitometry results for her hip and lumbar areas, and no fractures over the last 6 years of treatment. Ten months after the treatment with denosumab was stopped, a cascade of vertebral fractures, including some in unusual locations (third thoracic vertebra), and multiple rib fractures in a context of hypercalcemia, suggested possible malignancy. A complete evaluation, including systemic, biological, and biopsy analyses, ruled out this hypothesis. The hypercalcemia was associated with normal plasma phosphate and vitamin D concentrations, and a high parathyroid hormone level, with an abnormal fixation of the lower lobe of the thyroid on sesta-methoxy-isobutyl-isonitrile scintigraphy. Histological analysis of the excised parathyroid tissue revealed hyperplasia. The associated thyroidectomy (goiter) led to the discovery of a thyroid papillary microcarcinoma. Conclusions: We consider the consequences of this rebound effect, not only in terms of the major loss of bone density (return to basal values within 3 years) and the multiple disabling fracture episodes, but also in terms of the hypercalcemia observed in association with apparently autonomous tertiary hyperparathyroidism. Several cases of spontaneous reversion have been reported in children, but the intervention in our patient precluded any assessment of the possible natural course. The discovery of an associated thyroid neoplasm appears to be fortuitous. Better understanding of the various presentations of the rebound effect after stopping treatment with denosumab would improve diagnostic management of misleading forms, as in this case. Bisphosphonates could partially prevent this rebound effect.

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Effect of low dose denosumab on bone mineral density in postmenopausal women with osteoporosis after a transition from 60 mg dose: a prospective observational study

Khan

AbuAlrob

M’Hiri³

et al. 2023

Endocrine

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Introduction Denosumab is an effective antiresorptive molecule and reduces the risk of fracture in postmenopausal osteoporosis. Cessation of denosumab therapy however is associated with rapid declines in bone mineral density (BMD), rises in bone remodeling, and an increased risk of fracture. We evaluated the effect of low dose denosumab (30 mg every 6 months) on the prevention of bone loss following a switch from standard dose (60 mg of denosumab every 6 months) in a prospective observational study. Methods We recruited 114 women 50–90 years of age with postmenopausal osteoporosis at a moderate fracture risk without prior fragility fractures, who had been on denosumab 60 mg every 6 month. These women switched to low dose denosumab 30 mg every 6 months. Mean percentage change in lumbar spine (LS), femoral neck (FN), total hip (TH) and 1/3 distal radius (1/3RAD) BMD at 12 and 24 months were evaluated. Predictors for change in BMD were explored. Subgroup analysis for patients on denosumab 60 mg every 6 months for <3 years and for ≥3 years before switching to low dose denosumab 30 mg was evaluated. Results At 12 months following a switch from 60 mg to 30 mg of denosumab every 6 months we observed an increase in LS BMD mean percentage change (+2.03%, 95% CI 1.18–2.88, p < 0.001). BMD was stable at the hip and radial sites. Age was found to be a predictor of the mean percentage change in LS BMD for the overall sample. At 24 months, there was a further increase in LS BMD mean percentage change (+3.44%, 95% CI 1.74–5.12, p < 0.001), with stable BMD at other skeletal sites. The 12 month mean BMD percentage change at the LS (p = 0.015), FN (p < 0.001), TH (p < 0.001), and 1/3 RAD (p < 0.001) were found to be predictors of the 24 month mean BMD percentage change. No clinical fractures were reported during 24 months of follow up. Conclusion We observed stable BMD following a switch from denosumab 60 mg every 6 months to 30 mg every 6 months in this prospective observational study conducted in postmenopausal women at a moderate fracture risk

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Fracturas vertebrales múltiples tras la suspensión de tratamiento con denosumab: serie de diez casos

Cited by 6 publications

References 11 publications

Zoledronate for the Prevention of Bone Loss in Women Discontinuing Denosumab Treatment. A Prospective 2-Year Clinical Trial

Zoledronate for the Prevention of Bone Loss in Women Discontinuing Denosumab Treatment. A Prospective 2-Year Clinical Trial

Long-term follow up after denosumab treatment for osteoporosis – rebound associated with hypercalcemia, parathyroid hyperplasia, severe bone mineral density loss, and multiple fractures: a case report

Effect of low dose denosumab on bone mineral density in postmenopausal women with osteoporosis after a transition from 60 mg dose: a prospective observational study

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