INCREASED OSTEOCLASTOGENESIS IN PATIENTS EXPERIENCING VERTEBRAL FRACTURES FOLLOWING DENOSUMAB DISCONTINUATION

Bone and mineral researc

Increased osteoclastogenesis in patients with vertebral fractures following discontinuation of denosumab treatment

Bone and mineral researc

Bisphosphonate dose and incidence of fractures in postmenopausal osteoporosis

INTRODUCTION: The specific pharmacological properties of bisphosphonates, have raised concerns about their long-term effects on skeletal fragility that may be related to the total dose of bisphosphonate given. However, the effect of different doses on the incidence of osteoporotic fractures has not been adequately studied. METHODS: In this retrospective analysis, we investigated the effect of different doses of intravenous pamidronate given at 3-monthly intervals on the incidence of fractures in 92 women with severe postmenopausal osteoporosis. RESULTS: The risk of sustaining a new vertebral fracture on treatment was significantly increased by 32% for every prevalent vertebral fracture (OR: 1.32, CI: 1.05, 1.66; p=0.02). Patients with nonvertebral fractures received a significantly lower dose of pamidronate and their risk for these fractures increased by 25% for every prevalent fracture at baseline (OR: 1.25, CI: 1.01, 1.53; p=0.03). Patients who had received oral bisphosphonate before intravenous pamidronate had a significantly higher incidence of nonvertebral fractures which, however, did not hold true after adjustment for baseline BMD and prevalent fractures. CONCLUSIONS: In patients with established osteoporosis bone fragility during treatment with intravenous pamidronate is mainly determined by the severity of the disease, assessed by the presence and numbers of prevalent fractures, rather than the dose of the bisphosphonate or the rate of bone turnove

The Duration of Denosumab Treatment and the Efficacy of Zoledronate to Preserve Bone Mineral Density After Its Discontinuation

Context: Zoledronate is used to prevent bone loss following denosumab discontinuation but its efficacy differs among studies.Objective: To test if the duration of denosumab treatment affects the efficacy of subsequent zoledronate infusion.Methods: This multicenter, prospective cohort study, conducted at 2 Greek and 1 Dutch bone centers, included 47 postmenopausal women (n=47) who received a single zoledronate infusion 6 months after the last denosumab injection and then were followed for 1 year. Twenty-seven women received 6 denosumab injections (> 6 Group). The main outcome measure was changes in lumbar spine (LS) bone mineral density (BMD).Results: At 12 months LS-BMD values were maintained in the 6 Group (1.0 +/- 0.11 to 0.93 +/- 0.12 g/cm(2), P6 Group (-7.0%). In the whole cohort, the duration of denosumab treatment was negatively correlated with the percentage change of LS-BMD (r(s) = -0.669, P<0.001) but not with the change of femoral neck (FN)-BMD. Bone turnover markers increased in all patients 6 months following zoledronate administration with no difference between the 2 groups.Conclusion: The duration of denosumab treatment significantly affects the efficacy of subsequent zoledronate infusion to maintain BMD gains. Frequent follow-up of patients treated with denosumab longer than 3 years is advisable as additional therapeutic interventions may be needed.Diabetes mellitus: pathophysiological changes and therap

Acute phase response following intravenous zoledronate in postmenopausal women with low bone mass

Bone and mineral researc