Sustained Vertebral Fracture Risk Reduction After Withdrawal of Teriparatide in Postmenopausal Women With Osteoporosis

Lindsay, Robert; Scheele, Wim H.; Neer, Robert M.; Pohl, Gerhardt; Adami, Silvano; Mautalén, C.; Reginster, Jean‐Yves; Stepan, Jan J.; Myers, Steven; Mitlak, Bruce

doi:10.1001/archinte.164.18.2024

Cited by 287 publications

(190 citation statements)

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“…However, the hazard ratio between the 20 and 40 g groups was not significantly different. Our findings are in accordance with previous publications that showed continued vertebral fracture efficacy up to 18 months in women with postmenopausal osteoporosis (8) and up to 30 months in men with idiopathic or hypogonadal osteoporosis (13) after teriparatide treatment stopped. Furthermore, the magnitude of fracture risk reduction in this follow-up study is similar in magnitude to the reduction in relative risk of fracture in antiresorptive trials during treatment.…”

Section: Discussionsupporting

confidence: 93%

Sustained Nonvertebral Fragility Fracture Risk Reduction After Discontinuation of Teriparatide Treatment

Prince

Sipos

Hossain

et al. 2005

Journal of Bone and Mineral Research

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188

109

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A follow-up in 1262 women was conducted after the discontinuation of teriparatide. The hazard ratio for combined teriparatide group (20 and 40 µg) for the 50-month period after baseline was 0.57 (p = 0.002), suggesting a sustained effect in reducing the risk of nonvertebral fragility fracture.Introduction: Treatment with teriparatide [rhPTH(1-34)] 20 and 40 g once-daily subcutaneous dosing significantly reduced the risk of nonvertebral fragility fractures over a median exposure of 19 months. Materials and Methods: All participants in the Fracture Prevention Trial were invited to participate in a follow-up study. Prior treatment assignments were revealed, and patients were able to receive osteoporosis treatments without restriction.Results: Approximately 60% of the 1262 patients received an osteoporosis treatment at some time during follow-up, with greater use in the former placebo group than in the combined former teriparatide group (p < 0.05). The hazard ratios for nonvertebral fragility fractures in each teriparatide group relative to placebo were statistically significant for the 50-month period including treatment and follow-up (p < 0.03). In the follow-up period, the hazard ratio was significantly different between the 40 g and combined groups versus placebo but not for the 20 g group versus placebo. However, the 20 and 40 g groups were not different from each other. Kaplan-Meier analysis of time to fracture showed that the fracture incidence in the former placebo and teriparatide groups diverged during the 50-month period including teriparatide treatment and follow-up (p ‫ס‬ 0.009). Total hip and femoral neck BMD decreased in teriparatide-treated patients who had no follow-up treatment; BMD remained stable or further increased in patients who received a bisphosphonate after teriparatide treatment. Conclusions: While the study design is observational, the results support a sustained effect of teriparatide in reducing the risk of nonvertebral fragility fractures up to 30 months after discontinuation of treatment.

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Section: Discussionsupporting

confidence: 93%

Sustained Nonvertebral Fragility Fracture Risk Reduction After Discontinuation of Teriparatide Treatment

Prince

Sipos

Hossain

et al. 2005

Journal of Bone and Mineral Research

Self Cite

188

109

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“…10 On the basis of those results, we undertook a phase 3 trial that evaluated the effects of 1 year of romosozumab treatment on the risk of fracture among women with postmenopausal osteoporosis. Given evidence that bone mineral density is maintained or potentially increased after the transition from treatment with a boneforming agent to treatment with an antiresorptive agent, 12,13 we also assessed follow-on therapy with denosumab as sequential treatment for osteoporosis.…”

mentioning

confidence: 99%

Romosozumab Treatment in Postmenopausal Women with Osteoporosis

et al. 2016

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BACKGROUNDRomosozumab, a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. METHODSWe enrolled 7180 postmenopausal women who had a T score of -2.5 to -3.5 at the total hip or femoral neck. Patients were randomly assigned to receive subcutaneous injections of romosozumab (at a dose of 210 mg) or placebo monthly for 12 months; thereafter, patients in each group received denosumab for 12 months, at a dose of 60 mg, administered subcutaneously every 6 months. The coprimary end points were the cumulative incidences of new vertebral fractures at 12 months and 24 months. Secondary end points included clinical (a composite of nonvertebral and symptomatic vertebral) and nonvertebral fractures. RESULTSAt 12 months, new vertebral fractures had occurred in 16 of 3321 patients (0.5%) in the romosozumab group, as compared with 59 of 3322 (1.8%) in the placebo group (representing a 73% lower risk with romosozumab; P<0.001). Clinical fractures had occurred in 58 of 3589 patients (1.6%) in the romosozumab group, as compared with 90 of 3591 (2.5%) in the placebo group (a 36% lower risk with romosozumab; P = 0.008). Nonvertebral fractures had occurred in 56 of 3589 patients (1.6%) in the romosozumab group and in 75 of 3591 (2.1%) in the placebo group (P = 0.10). At 24 months, the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo group after each group made the transition to denosumab (0.6% [21 of 3325 patients] in the romosozumab group vs. 2.5% [84 of 3327] in the placebo group, a 75% lower risk with romosozumab; P<0.001). Adverse events, including instances of hyperostosis, cardiovascular events, osteoarthritis, and cancer, appeared to be balanced between the groups. One atypical femoral fracture and two cases of osteonecrosis of the jaw were observed in the romosozumab group. CONCLUSIONSIn postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and, after the transition to denosumab, at 24 months. The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year. (Funded by Amgen and UCB Pharma; FRAME ClinicalTrials.gov number, NCT01575834.)

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“…(32) Vertebral fracture has less regional variations than hip fractures in osteoporosis and this risk can be reduced by medication. (6,(35)(36)(37)(38)(39) The higher mortality rate in patients with vertebral fractures may also reflect their poor health status. (40)(41)(42) The present study for the first time correlates subsequent primary stroke with osteoporotic vertebral fracture.…”

Section: Discussionmentioning

confidence: 99%

Hospitalized osteoporotic vertebral fracture increases the risk of stroke: A population-based cohort study

Chen

Huang

et al. 2012

Journal of Bone and Mineral Research

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The association between osteoporosis and cardiovascular diseases has been demonstrated. Higher cardiovascular risk has also been correlated with vertebral fractures. However, the association between osteoporotic vertebral fracture and the possibly higher risk of stroke remains uncertain. This study aimed to evaluate the incidence, risk, and type of stroke in patients with osteoporotic vertebral fracture. Patients with osteoporotic vertebral fracture were identified (n ¼ 380) and 10 age-and sex-matched controls per case (comparison group, n ¼ 3795) were chosen from a nationwide representative cohort of 999,997 people from 1998 to 2005. Both groups were followed-up for stroke events for 3 years, matched by propensity scores with adjustments for covariates such as comorbidities (ie, hypertension, diabetes, arrhythmia, or coronary heart diseases) and exposure to medications (ie, aspirin, lipid lowering drug, or nitrates), and assessed by Kaplan-Meier and Cox regression analyses. The incidence rate of stroke in the osteoporotic vertebral fracture group (37.5 per 1000 person-years; 95% confidence interval [CI], 27.5-51.2) was significantly higher than in the comparison group (14.0 per 1000 person-years; 95% CI, 12.0-16.4, p < 0.001). Stroke was more likely to occur in the osteoporotic vertebral fracture patients than in the normal controls (crude hazard ratio [HR] 2.68, 95% CI 1.89-3.79, p < 0.001; adjusted HR 2.71, 95% CI 1.90-3.86, p < 0.001). In conclusion, patients with osteoporotic vertebral fracture have a higher risk of stroke (ie, both ischemic and hemorrhagic) and require stroke prevention strategies. ß

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Sustained Vertebral Fracture Risk Reduction After Withdrawal of Teriparatide in Postmenopausal Women With Osteoporosis

Abstract: Vertebral fracture risk reduction by teriparatide administration persists for at least 18 months after discontinuation of therapy.

Cited by 287 publications

References 13 publications

Sustained Nonvertebral Fragility Fracture Risk Reduction After Discontinuation of Teriparatide Treatment

Sustained Nonvertebral Fragility Fracture Risk Reduction After Discontinuation of Teriparatide Treatment

Romosozumab Treatment in Postmenopausal Women with Osteoporosis

Hospitalized osteoporotic vertebral fracture increases the risk of stroke: A population-based cohort study

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