Amendment N°1: The non-selection criterion “Participant belonging to any of the following categories: incarcerated persons, subjects in an emergency situation, patients with severe mental disorders, patients legally incapacitated” has been completed by the mention “patients who are placed in an institution following official or judicial order”. This has been added in the corresponding section of the protocol. The criterion for the discontinuation of the study has been detailed by adding that the study can be prematurely interrupted in case of any new findings, which can modify the benefit/risk ratio in patients. The withdrawal criteria have been detailed by adding that the study may be prematurely discontinued for a participant for one of the following reasons: adverse events, considered or not as related to the study drug or to the study procedures and which could modify the benefice/risk ratio for the patient according to the investigator’s opinion, protocol deviation, non medical reason, lost to follow-up. The study must imperatively be discontinued for a participant in case of: Lack of efficacy being defined as BMD decrease ≥5% (e.g relative change vs.baseline) at one or more sites (lumbar L1-L4, femoral neck or total hip) or two or more new osteoporotic non traumatic major fractures (vertebral, hip or humerus). Information about the packaging and the numbering of the supplementation (Calcimagon®500 and Vigantoletten®1000) has been updated. The originally planned pack size of the supplementation was changed, the number of boxes of Calcimagon®500 and Vigantoletten®1000 given to the patient has been updated consequently. For a clear identification of the supplementation, it will now be numbered. A 6 digits number independent of the patient number will identify this supplementation.

Amendment N°2: The selection criteria have been modified to select patients with “Osteoporosis with previous bisphosphonate therapy for at least 36 continuous months* before study entry with oral alendronate (70 mg once weekly or 10 mg daily), oral risedronate (35mg once weekly or 5mg daily), or oral ibandronate (150mg once monthly) and last bisphosphonate intake within 2 months before study entry”. *An adaequate previous bisphosphonate treatment requires an estimated overall medication posession ratio (MPR) of at least 80% for the last 36 months of bisphosphonate treatment, in general, as well as an estimated recent MPR of at least 80% for the last 12 months before study entry, in particular. The pQCT exams will be performed at M012 in duplicate. The total irradiation for the whole study is 27 μSv with a maximal total irradiation in case of 3 scans per site at each visit is 97 μSv, since repeated measurements might be needed due to movement artifacts or mandatory relocation of a scan. Following the BfS (Bundesamt für Strahlenschutz) approval, the irradiation dose for the hr-QCT measurement is estimated at 5.1 mSv. The investigator has to evaluate and confirm patients’ data by documenting them directly in the patient’s medical file. Moreover the recruitment process and the documentation of the data used for clinical assessment is described in the internal procedure of the site. The conditions of sampling for the safety biological parameters have been changed, fasting condition is not necessary anymore. Blood samples should be collected before 10:00 am on the morning of the visit. Only CK-MB isoenzyme will be measured in case of CK above upper limit of the reference range. The Sponsors address is modified to 50 rue Carnot, 92284 Suresnes cedex, France in the Protocol.

Amendment N°3: The non-selection criteria have been updated in the study summary sheet and in the protocol. The non-selection criteria concerning venous thrombotic events has been rephrased as follows: “Current or previous venous thromboembolic events, including deep vein thrombosis and pulmonary embolism, or patients at high risk of venous thromboembolism”. A new non-selection criteria was introduced: “Temporary or permanent immobilization due to e.g. post-surgical recovery or prolonged bed rest” The following treatment withdrawal criteria have been added in the Protocol: Treatment should be temporarily or permanently discontinued as soon as possible in the event of an illness or a condition leading to immobilization (for example post-surgical recovery or prolonged best rest). Therapy should not be restarted until the initiating condition has resolved and the patient is fully mobile. Treatment should also be immediately and permanently discontinued in the following cases: a) venous thromboembolic events; b) presence of symptoms or signs of Stevens Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN; e.g. progressive skin rash often with blisters or mucosal lesions) or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS; e.g. rash, fever,eosinophilia and systemic involvement [e.g. adenopathy, hepatitis, interstitial nephropathy, interstitial lung disease]). The following precision concerning management of cases of severe hypersensitivity reaction has been added in the protocol, under paragraph 12 “Safety assessments”: In all participants experiencing severe hypersensitivity reaction type DRESS, TEN or SJS, the investigator in charge of the patient will receive a letter from the Sponsor with recommendation for additional investigations. A careful monitoring of these events will have to be performed.

Amendment N°4: The title of the study has been modified to “A 24 months, prospective, randomized, double-blind study to assess the effect of daily oral administration of 2 g of strontium ranelate versus placebo on bone mineral density in postmenopausal osteoporotic women previously treated with bisphosphonates”. The recruitment period has been extended by 9 months. Thus, the Study completion date (LVLP) has been postponed to September 2015 in the Study Summary Sheet. The selection criteria have been modified to select patients with “Osteoporosis with previous bisphosphonate therapy before study entry for at least 30 months among the last 5 years, and last bisphosphonate intake within 6 months before study entry. Bisphosphonate therapy includes oral alendronate (70 mg once weekly or 10 mg daily), oral risedronate (35 mg once weekly or 5 mg daily), oral ibandronate (150 mg once monthly) or intravenous ibandronate (3 mg/3 months). *An adequate previous bisphosphonate treatment requires an estimated recent medication possession ratio (MPR) of at least 75% in the last year of bisphosphonate treatment.

Amendment N°5: The study is now a multicentric study. The wording has been adapted within the all protocol (i.e. “the center” became “each center”). The following sections have been updated: Study summary sheet: Coordinator(s), Study centre(s), Methodology and Statistical methods. Administrative structure of the study: International Coordinator, National Coordinators and Structure responsible for local management of the study. Procedure for an event requiring immediate notification: Persons to be contacted in ICTR. Measures to minimize bias. Statistical analysis. Hr-QCT and p-QCT will not be performed in new countries. Hr-QCT will be performed only in the International Coordinator’s centre and p-QCT will be performed only in Germany. Thus, the following sections have been updated: Study summary sheet: Secondary objectives, Main non-selection/non-inclusion criteria and Secondary efficacy criteria. Investigational schedule. Medical and therapeutic criteria. Assessment of bone geometry and bone strength by p-QCT: Method of investigation and measurement time. Hr-QCT Th12 (spiral CT): Method of investigation. Statistical analysis concerning p-QCT and Hr-QCT. BMD and VFA assessment will be performed by a Lunar® or a Hologic® device. Thus, the following sections have been updated: Assessment of BMD measurement by DXA. Vertebral Fracture Assessment. Local specificities of the International Coordinator’s centre have been implemented with general information to take into account all additional centres. Thus, the following sections have been updated: Study summary sheet: Main non-selection/non-inclusion criteria. Non sponsor parties. Investigational schedule. Products administered. Treatment management. Previous bisphosphonate therapy. Participant information and informed consent. Other modifications: The criteria and procedure for patient withdrawal have been precised, typing error regarding the composition of the placebo has been deleted. Administrative sponsor updated.

Amendment N°6: Selection criteria have been updated in order to specify that selected patients should have a high risk of fracture. The non-selection criteria have been also updated. The non-selection criterion concerning cardiac ischaemic events has been introduced: “Current or past history of ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease”. Patients with not adequately controlled hypertension were already not selected in the study. The following treatment withdrawal criteria have been added: “Treatment should be permanently discontinued as soon as possible in the event of uncontrolled hypertension, or in the event of the treatment is considered as no longer appropriate by the investigator e.g. in case of significant cardiovascular risk factors.”, “Treatment should be immediately and permanently discontinued in the case of current or past ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease.” Before starting treatment and at regular intervals, patients should be evaluated with respect to cardiovascular risk. Patients with significant risk factors for cardiovascular events will be closely monitored, and initiation and continuation of the treatment will be carefully assessed based on the individual patient’s overall risks. For this reason, additional safety measurements have been added to the protocol: additional blood pressure measurements at M003, M006 and M018 visits, and blood biological parameters (HDL and LDL cholesterol, triglycerides, glycaemia, under fasting conditions) at the selection, M006, M012, M018 and M024 visits. Thus, the following sections have been updated: Investigational schedule, Safety measurements, Clinical safety, Biological safety, Safety. The procedure to be followed in case of premature discontinuation of the study has been adapted. The last visit last patient date, list of investigation and administrative sponsor(s) parties have been updated.

Amendment N°7: only for BEL, DEU, FRA , HUN and POL. Calicmagon®500 is replaced by Orocal®500, 60 tablets per box. Thus, the following sections have been updated: - Study summary sheet: Precaution with supplementations. - Products administered (Paragraph 8.4.1.). - Treatment management (Paragraph 8.4.2.). - Treatments administered (Paragraph 10.1.). - Previous and concomitant treatments (Paragraph 10.3.). Paragraph 8.4.1. (Products administered) has also been updated regarding the number of tablets in each box of Vigantoletten®1000. The last visit last patient date has been updated in the study summary sheet. Paragraph 12.2.2. has been updated to inform that results of all biological safety parameters are reported in the e-CRF by the investigator. A typing error has been corrected in Paragraph 8.3..

Amendment N°8: only for AUT. The selection criteria have been updated in order to specify that selected patients should have taken bisphosphonate therapy for at least 60 months before their participation in the study. Calicmagon®500 is replaced by Orocal®500, 60 tablets per box. Thus, the following sections have been updated: - Study summary sheet: Precaution with supplementations. - Products administered (Paragraph 8.4.1.). - Treatment management (Paragraph 8.4.2.). - Treatments administered (Paragraph 10.1.). - Previous and concomitant treatments (Paragraph 10.3.). Paragraph 8.4.1. (Products administered) has also been updated regarding the number of tablets in each box of Vigantoletten®1000. The last visit last patient date has been updated in the study summary sheet. Paragraph 12.2.2. has been updated to inform that results of all biological safety parameters are reported in the e-CRF by the investigator. A typing error has been corrected in Paragraph 8.3..