Sequential Therapies After Osteoanabolic Treatment

Study Overview
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Brief Summary
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12-month prospective, open-label, multicenter, international, observational study evaluating sequential treatments after osteoanabolics

Detailed Description
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Caucasian women with severe postmenopausal osteoporosis who have completed their course with romosozumab or teriparatide will be assigned to one of the following 3 options: i) zoledronate 5mg infusion or ii) denosumab subcutaneous injections or iii) teriparatide (for those previously treated with romosozumab) or romosozumab (for those previously treated with teriparatide). Endpoints: Primary: BMD changes at the lumbar spine at 12 months. Secondary: i) BMD changes at the non-dominant femoral neck and total hip at 12 and 24 months; ii) changes at levels of bone turnover markers throughout the study; iii) incident fractures: vertebral (clinical and morphometric identified on VFA scans) and non-vertebral

Official Title
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Efficacy of Sequential Therapies After Osteoanabolic Treatment in Postmenopausal Women With Severe Osteoporosis: the Sequential Treatment After Romosozumab and Teriparatide (START) Study

Conditions
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Osteoporosis, Postmenopausal

Intervention / Treatment
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* Drug: Zoledronate
* Drug: Denosumab
* Drug: Teriparatide
* Drug: Romosozumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Postmenopausal women treated with severe osteoporosis completing their course with romosozumab or teriparatide Exclusion Criteria: a bone disease other than postmenopausal osteoporosis use of medications other than romosozumab or teriparatide affecting bone metabolism during the last 12 months before entering the study creatinine clearance <60 mL/min/1.73 m2 liver failure any type of cancer uncontrolled endocrine diseases serum 25-hydroxy vitamin D (25-OHD) concentrations lower than 20 ng/mL (50 nmol/L) hypersensitivity to denosumab or zoledronate or teriparatide or romosozumab or any of the excipients

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Romo-Zol group<br>Postmenopausal women treated with romosozumab for 12 months will receive a single zoledronate infusion (5mg) at 1 month after the last romosozumab dose | Drug: Zoledronate<br>* intravenous infusion<br>* Other names: zoledronic acid; zolendronate;|
| Romo-Dmab group<br>Postmenopausal women treated with romosozumab for 12 months will receive subcutaneous denosumab injections (60mg) bi-annually for 12 months starting at 1 month after the last romosozumab dose | Drug: Denosumab<br>* subcutaneous injection<br>* Other names: Dmab;|
| Romo-TPTD group<br>Postmenopausal women treated with romosozumab for 12 months will receive daily injections of teriparatide 20μg for 12 months starting at 1 month after the last romosozumab dose | Drug: Teriparatide<br>* subcutaneous injection<br>* Other names: TPTD;|
| TPTD-Zol group<br>Postmenopausal women treated with teriparatide for 24 months will receive a single zoledronate infusion (5mg) at 1 month after the last romosozumab dose | Drug: Zoledronate<br>* intravenous infusion<br>* Other names: zoledronic acid; zolendronate;|
| TPTD-Dmab group<br>Postmenopausal women treated with teriparatide for 24 months will receive subcutaneous denosumab injections (60mg) bi-annually for 12 months | Drug: Denosumab<br>* subcutaneous injection<br>* Other names: Dmab;|
| TPTD-Romo group<br>Postmenopausal women treated with teriparatide for 24 months will receive month injections of romosozumab for 12 months | Drug: Romosozumab<br>* subcutaneous injection<br>* Other names: Romo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lumbar spine bone mineral density | bone mineral density changes at the lumbar spine at 12 months measured by dual-energy absorptiometry (DXA) | baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| femoral neck bone mineral density | bone mineral density changes at the femoral neck at 12 months measured by dual-energy absorptiometry (DXA) | baseline to 12 months | 
| total hip bone mineral density | bone mineral density changes at the total hip at 12 months measured by dual-energy absorptiometry (DXA) | baseline to 12 months | 
| P1NP | bone turnover (formation) marker | baseline, 3 months, 6 months, 12 months | 
| CTx | bone turnover (resorption) marker | baseline, 3 months, 6 months, 12 months | 
| Fractures | incident fractures: vertebral (clinical and morphometric identified on VFA scans) and non-vertebral | 12 months |