Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Zometa, Zoledronate, ZOL446
zoledronic acid · 41 trials · 28 indications
Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) to demonstrate that zoledronic acid given long-term, over an additional 12 months from the Core study (CZOL446H2337), is safe for the treatment of osteoporotic children treated with glucocorticoids through the monitoring of relevant clinical and laboratory safety parameters.
Lumbar Spine Bone Mineral Density (BMD) Z-score was determined by the central imaging vendor before first treatment and at Month 12. The methods to be used to measure Lumbar Spine BMD Z-score were described in the respective DXA Manuals provided by central imaging vendor. Positive changes from baseline indicated an improvement in condition.
Bone Mineral Density (BMD) measured by dual energy x-ray absorptiometry (DXA). DXA consists of two X-ray beams with different energy levels that are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Percentage change from Year 6 = 100\*(Year 9 - Year 6)/Year 6.
Vertebral fracture (VF) was assessed based on morphometry. QM(quantitative morphometry) incident VF(QM positive) is defined by at least 20% decrease in vertebral height of at least 4mm. If participant had QM positive at any vertebrae at any visit, x-rays from visits for participants were evaluated using Genant semi-quantitative method for VF assessment: Grade1 Mild VF is defined as 20-24% decrease in anterior, middle, and/or posterior vertebral height. Grade2 moderate VF is defined as 25-40% decrease in vertebral height. Grade3 Severe VF is defined as more than 40% decrease in vertebral height
BMD measurements of the lumbar spine (L1-L4) by Dual X-ray absorptiometry (DXA) were performed on all patients at screening, and Weeks 13, 26, and 52 (or early termination). Every attempt was made to obtain the BMD measurements at the scheduled visit. If this was not possible, a BMD measurement ± 7 days from the scheduled visit was obtained. For the Final DXA at Week 52, the window was 10 - 15 days prior to the final study visit. BMD scans were acquired locally and all results sent to a central reader for evaluation.
The level of bone activity as measured by NTx over the course of 12 months was assessed using the standardized area under the curve. Blood samples were collected after an overnight fast of at least 8 hours between 7:00 and 11:00 AM at Screening and Months 1.5, 3, 6, 9, and 12 months after baseline. Serum was analyzed at a central lab using commercially available ELISA kits. Standardized AUC was calculated by the AUC divided by the number of days the patient participated in the study.
The level of bone activity as measured by NTx over the course of 12 months was assessed using the standardized area under the curve. Blood samples were collected after an overnight fast of at least 8 hours between 7:00 and 11:00 AM at Screening and Months 1.5, 3, 6, 9, and 12 months after baseline. Serum was analyzed at a central lab using commercially available ELISA kits. Standardized AUC was calculated by the AUC divided by the number of days the patient participated in the study.
The SMR was computed by summing all Skeletal Related Event(s) (SREs)which occurred during the observation period and dividing it by the ratio "days of observation period / 365.25", for each participant. SRE was defined as: pathologic bone fracture, spinal cord compression, surgery to bone both curative and prophylactic, radiation therapy to bone, or hypercalcemia of malignancy. SMR (years) = 365.25 x SMR(days) where SMR (days) = total number of SREs / total SRE risk period (days). Risk period for SMR was computed as the days from randomization date to the date of last visit.
An SRE was defined as a pathologic fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone or surgery to bone.
Skeletal-related event free survival is the time from randomization until the first detected Skeletal Related Event (SRE). Patients who were still SRE-free at 18 months were censored.
Bone mineral density (BMD) by DXA at lumbar spine (L2-L4); DXA assessments of the BMD at dual hips. (BMD). Two X-ray beams with different energy levels are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone.
Bone mineral density (BMD) at lumbar spine (L2-L4) by T-score. Your T-score is the number of units that your bone density is above or below the average. -1 and above-bone density is considered normal; Between -1 and -2.5-is a sign of osteopenia, a condition in which bone density is below normal and may lead to osteoporosis. -2.5 and below-indicates that it is likely osteoporosis.
Bone mineral density (BMD) at lumbar spine (L2-L4) measured by Z-score. If Z-score is -2 or lower, it may suggest that something other than aging is causing abnormal bone loss.
Bone mineral density (BMD) at lumbar spine (L2-L4) measured by using Lunar or Hologic dual-energy X-ray absorptiometry (DXA) Instruments. Measurements were done in the lumbar vertebrae (L2-L4)
The primary efficacy variable was the percentage change in BMD of the femoral neck as measured by dual x-ray absorptiometry (DXA) at Year 6 relative to Year 3. It was derived as 100 \*(femoral neck BMD at Year 6 - femoral neck BMD at Year 3) / (femoral neck BMD at Year 3).
Progression-free survival is defined as the time from randomization to the date of the first documented progression or recurrence of disease or death from any cause. Time to disease progression (TTP) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines with evaluations every 3 months.
Progression-free survival is defined as the time from randomization to the date of the first documented progression or recurrence of disease or death from any cause. Time to disease progression (TTP) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines with evaluations every 3 months.
Percentage of Participants with the Progression-free survival events: disease progression and death. Time to disease progression (TTP) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines with evaluations every 3 months.
The percentage change in lumbar spine BMD at Month 24 relative to baseline was derived as 100 x (lumbar spine BMD at 24 Month - lumbar spine BMD at baseline) / (lumbar spine BMD at baseline).
Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100.
Time to first skeletal related event (SRE) was defined as the time from randomization to first skeletal event. Skeletal events are defined as radiation to bone, clinical fracture, surgery to bone and spinal cord compression and death due to prostate cancer. The median with 95% CI was estimated using the Kaplan Meier method.
Bone Mineral Density (g/cm\^2) of the Lumbar Spine (L2-L4) as measured by energy x-ray absorptiometry (DXA).
Bone mineral density (BMD) measurements were assessed by dual energy x-ray absorptiometry (DXA). The DXA devices of participating sites were cross-calibrated and the DXA results were compiled and analyzed by a central reader. Percent change = 100\*((BMD at Month 12 - Baseline BMD)/Baseline BMD)). Missing data at month 12 were imputed by using the last observation carried forward (LOCF) method. Post-baseline non-missing data from month 6 were carried forward to month 12. Data prior to month 6 were not carried forward.
A therapeutic response was defined as a reduction of at least 75% from baseline (Visit 1) in serum alkaline phosphatase (SAP) excess (difference between measured level and midpoint to the normal range) or normalization of SAP at the end of six months.
Therapeutic response is defined as a reduction of at least 75% from baseline (Visit 1) in total serum alkaline phosphatase excess (difference between measured level and midpoint to the normal range) or normalization of serum alkaline phosphatase at the end of six months.
DFS is defined as time from randomization to first occurrence of a local, regional, or distant recurrence, second primary carcinoma (including contralateral breast cancer), or death from any cause
DFS is defined as time from randomization to first occurrence of a local, regional, or distant recurrence, second primary carcinoma (including contralateral breast cancer), or death from any cause
Median change in disseminated tumor cells (DTCs)/mL from baseline after 24 months
BMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer.
| Arm | Type | Description |
|---|---|---|
| Chemotherapy + zoledronic acid | EXPERIMENTAL | - |
| chemotherapy | ACTIVE_COMPARATOR | - |
| Zoledronic acid | EXPERIMENTAL | Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid |
| Placebo | PLACEBO_COMPARATOR | Twice yearly i.v of infusion of Placebo (similar dosing as active drug) |
| Zoledronic acid plus teriparatide | ACTIVE_COMPARATOR | Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks. |
| Placebo zoledronic acid plus teriparatide | ACTIVE_COMPARATOR | Placebo zoledronic acid 100 mL intravenous (i.v.) (once at randomization) plus teriparatide 20 μg (daily subcutaneous injections administered concurrently through 52 weeks). Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks. |
| Zoledronic acid 5 mg | EXPERIMENTAL | Patients received zoledronic acid 5 mg in 100 ml solution in a 15 minute intravenous (iv) infusion once per year. The peripheral iv infusion was preceded by and followed by a 10 ml normal saline flush of the intravenous line. In addition to study therapy, all participants received 1200 mg elemental calcium and 800 IU of vitamin D daily. Calcium and vitamin D were supplied in a chewable tablet that was to be taken twice daily. |
| Alendronate 70 mg | ACTIVE_COMPARATOR | Patients received an alendronate 70 mg tablet once weekly with 200 ml of tap water in the morning on an empty stomach at least 30 minutes before the first meal. Patients were to remain in an upright position for 30 minutes after swallowing the tablet. In addition to study therapy, all participants received 1200 mg elemental calcium and 800 IU of vitamin D daily. Calcium and vitamin D were supplied in a chewable tablet that was to be taken twice daily. |
| Every 3 months | EXPERIMENTAL | Zoledronic acid as a 15-minute (at least) intravenous (i.v.) infusion every three months. The dose of study drug will be the same administered before the study entry, that is 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized patients will receive a maximum of 4 infusions in this group. |
| Every 4 weeks | EXPERIMENTAL | Zoledronic acid as a 15-minute (at least) intravenous (i.v.) infusion every 4 weeks. The dose of study drug will be the same administered before the study entry, that is 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Patients randomized to this group will receive up to 12 infusions. |
| Zoledronic acid every (q) 4 weeks | EXPERIMENTAL | Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. |
| Zoledronic acid q 12 weeks | EXPERIMENTAL | Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind. |
| Placebo / zoledronic acid | EXPERIMENTAL | Participants randomized to this arm received placebo but the arm was later dropped and participants in this arm were swithced to the zoledronic acid q 4 weeks according to a study amendment. |
| Early Group | EXPERIMENTAL | Zoledronic acid 4 mg i.v. infusion every 4 weeks, commencing at Baseline. |
| Delayed group | EXPERIMENTAL | Zoledronic acid 4 mg i.v. infusion every 4 weeks, commencing no sooner than 12 months after their baseline visit, and not until they have had three rises in PSA level from Baseline, one of which must be a least 10 ng/mL greater than the baseline Serum Prostate-specific Antigen (PSA) level. |
| Zometa | EXPERIMENTAL | Zoledronic acid 4mg as a 15-minute infusion every 3 months for a treatment period of 24 months (total of 8 infusions). |
| zoledronate | EXPERIMENTAL | - |
| Zoledronic Acid 6 | EXPERIMENTAL | Patients who received Zoledronic acid for 3 years in the core study (CZOL446H2301; NCT00049829) received a single intravenous infusion of 5 mg Zoledronic acid once a year for 3 years (at Months 36, 48 and 60) in this extension study for a total of 6 years of treatment. |
| Zoledronic Acid 3 Placebo 3 | PLACEBO_COMPARATOR | Patients who were treated with Zoledronic acid for 3 years in the core study received a single intravenous matching Placebo infusion once a year for 3 years in this extension study. |
| Placebo 3 Zoledronic Acid 3 | EXPERIMENTAL | Patients who were treated with placebo for 3 years in the core study received 5 mg Zoledronic acid in a single intravenous infusion once a year for 3 years (at Months 36, 48 and 60) in this extension study. |
| Control | OTHER | No investigational treatment. If a participant developed bone metastases, treatment was started with Zoledronic acid 4 mg intravenous infusion over at least 15 minutes every 3 to 4 weeks until 24 months from the date of study entry had elapsed. |
| ZOL446 (zoledronic acid) | EXPERIMENTAL | - |
| Zoledronic Acid 2x5 mg | EXPERIMENTAL | Zoledronic acid 5 mg intravenous (i.v.) given at randomization and Month 12 |
| Zoledronic Acid 1x5 mg | EXPERIMENTAL | Zoledronic acid 5 mg intravenous (i.v.) given at randomization and placebo at Month 12 |
| Zometa® | EXPERIMENTAL | 4mg monthly for 12 months from date of first chemotherapy dose |
| no further treatment | NO_INTERVENTION | Control arm; no further treatment. Follow-up monthly for 12 months from date of first chemotherapy dose |
| Upfront Zoledronic Acid | EXPERIMENTAL | Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1 |
| Delayed Zoledronic Acid | EXPERIMENTAL | Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1 |
| Zoledronic acid + androgen deprivation therapy | EXPERIMENTAL | 4mg by IV over 15 minutes every 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progression on blinded treatment before having a skeletal event may continue on open label Zoledronic acid (4 mg by IV over 15 minutes every 3 weeks). |
| Placebo + androgen deprivation therapy | ACTIVE_COMPARATOR | Placebo bu IV over 15 minutes for 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progress on blinded treatment before having a skeletal event may continue on open label Zoledronic acid. |
| Zoledronic Acid upfront | EXPERIMENTAL | Participants in the upfront arm received zoledronate 4 mg i.v. on Day 1 and every 6 months until disease progression (recurrence) or the end of study. Participants also received Letrozole 2.5 daily plus calcium (1000-1200 mg) and vitamin D (400-800 IU) daily. |
| Zoledronate delayed-start | EXPERIMENTAL | In lieu of a placebo arm, which was considered unethical for this trial, a delayed start arm was used. Participants who met certain clinical criteria indicating risk of lumbar spine or total hip fracture, or experienced clinical fracture unrelated to trauma or any asymptomatic fracture discovered at the Month 36 scheduled visit, were started on zoledronate 4 mg i.v. and for every 6 months until disease progression (recurrence) or end of study. Participants also received Letrozole 2.5 daily plus calcium (1000-1200 mg) and vitamin D (400-800 IU) daily. |
| Zoledronic acid and placebo to risedronate | EXPERIMENTAL | Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period. |
| Risedronate and placebo to zoledronic acid | ACTIVE_COMPARATOR | Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period. |
| AZ (Arimidex+Zoledronate) | ACTIVE_COMPARATOR | Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid) |
| TZ (Tamoxifen+Zoledronate) | ACTIVE_COMPARATOR | Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid) |
| AC (Arimidex Control) | ACTIVE_COMPARATOR | Study Drug Arimidex (Anastrozole) |
| TC (Tamoxifen Control) | ACTIVE_COMPARATOR | Study Drug Nolvadex (Tamoxifen) |
| Active Zoledronic Acid & Placebo Alendronate | EXPERIMENTAL | Group 1 will receive an infusion of active zoledronic acid 5 mg during the first 4 weeks after transplantation. Placebo alendronate 70 mg once weekly will be initiated at the same time as the first zoledronic acid infusion. |
| Placebo Zoledronic Acid & Active Alendronate | EXPERIMENTAL | Group 2 will receive an infusion of placebo zoledronic acid during the first 5 weeks after transplantation. Active alendronate 70 mg once weekly will be initiated at the same time as the placebo infusion. |
| Test Group | EXPERIMENTAL | Zometa (zoledronic acid) 4 mg over 15 min IV infusion, every 4 week Anti-neoplastic therapy .Patients can receive concomitant cycles of chemotherapy or radiotherapy. |
| Contorl Group | NO_INTERVENTION | Anti-neoplastic therapy alone. Patients can receive concomitant cycles of chemotherapy or radiotherapy. |
| Zometa q 4 weeks | EXPERIMENTAL | - |
| Zometa q 12 weeks | ACTIVE_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| cisplatin | DRUG | - |
| doxorubicin hydrochloride | DRUG | - |
| etoposide | DRUG | - |
| ifosfamide | DRUG | - |
| methotrexate | DRUG | - |
| zoledronic acid | DRUG | - |
| conventional surgery | PROCEDURE | - |
| Placebo | DRUG | intravenous infusion |
| Zoledronic acid 5 mg iv | DRUG | Zoledronic acid 5 mg iv given once a year. |
| Teriparatide | DRUG | Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. Each pre-filled delivery device is filled with 3.3 mL to deliver 3 mL. Each mL contains 250 μg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetate acid, 0.10 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3.0 mg Metacresol, and water for injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4. Each cartridge pre-assembled into a pen device delivers 20 μg of teriparatide per dose each day for up to 28 days. |
| Zoledronic acid 5 mg solution | DRUG | Zoledronic acid was supplied as a concentrate of 5.33 mg zoledronic acid monohydrate in a 100 ml solution. 5.33 mg zoledronic acid monohydrate equals 5 mg zoledronic acid. |
| Alendronate 70 mg tablets | DRUG | Patients received an alendronate 70 mg tablet once weekly with 200 ml of tap water in the morning on an empty stomach at least 30 minutes before the first meal. |
| Calcium/Vitamin D | DRUG | Combined elemental calcium / vitamin D chewable tablets. Participants took 2 tablets a day, for a daily dose of calcium 1200 mg/vitamin D 800 IU. |
| Androgen Deprivation Therapy (ADT) | DRUG | Androgen deprivation therapy (ADT) was to be administered according to institutional protocols, in accordance with relevant prescribing information. The type and duration of androgen deprivation was at the discretion of the treating specialist, and could include orchiectomy where this would normally have been performed. Androgen deprivation therapy was provided by the investigational center, or obtained by the patient from usual sources. Anti-androgen monotherapy and intermittent ADT were excluded in the first 12 months of the study. |
| Zoledronic acid 4 mg | DRUG | Zoledronic acid 4 mg in 5 mL concentrated solution prepared with 100 mL calcium free infusion solution (0.9 % sodium chloride or 5% glucose solution). |
| Taxotere | DRUG | - |
| Carboplatin | DRUG | - |
| Letrozole | DRUG | Letrozole tablets 2.5 mg/day/taken orally for 5 years. |
| androgen deprivation therapy | DRUG | Patients concurrently enrolled on the Phase III study of intermittent androgen deprivation in patients with stage D2 prostate cancer will receive androgen deprivation therapy per SWOG-9346. All other patients will receive androgen deprivation therapy at a standard dose and schedule throughout the study. |
| GnRH agonist | DRUG | Patients concurrently enrolled on the Phase III study of intermittent androgen deprivation in patients with stage D2 prostate cancer will receive the GnRH agonist per SWOG-9346. All other patients will receive GnRH agonist at a standard dose and schedule throughout the study. |
| Calcium supplement | DIETARY_SUPPLEMENT | Patients will receive 500 mg by mouth daily of a calcium supplement or a combination tablet containing approximately 500 mg elemental calcium and 400-500 IU vitamin D by mouth daily. |
| Vitamin D | DIETARY_SUPPLEMENT | Patients will receive a multivitamin tablet containing 400-500 IU vitamin D by mouth daily or a combination tablet containing approximately 500 mg elemental calcium and 400-500 IU vitamin D by mouth daily. |
| placebo to zoledronic acid | DRUG | 5 mL of sterile water for infusion |
| Risedronate | DRUG | 30mg oral tablets overencapsulated to match the placebo capsules |
| Placebo to risedronate | DRUG | oral capsules |
| Calcium and vitamin D supplements | DRUG | Calcium and vitamin D supplements were supplied |
| Calcium and Vitamin D | DIETARY_SUPPLEMENT | Calcium and vitamin D supplements were supplied. |
| tamoxifen | DRUG | 20 mg/d |
| anastrozole | DRUG | 1 mg/d |
| goserelin | OTHER | 3.6 mg goserelin subcutaneously every 28 days |
| quality-of-life assessment | PROCEDURE | - |
| Alendronate | DRUG | Alendronate 70 mg will be taken once a week in the morning at least 30-60 minutes before first meal |
| Placebo Zoledronic Acid | OTHER | Infusion of placebo zoledronic acid during the first 5 weeks after transplantation |
| Placebo Alendronate | OTHER | Placebo alendronate 70 mg once weekly |
| Zometa (zoledronic acid) | DRUG | Zometa 4 mg IV infusion every 4 weeks for 24 months. Co-administration with Zometa: Calcium 500 mg + vitamin D 400-500 IU daily |
Inclusion Criteria * Histologically confirmed high-grade osteosarcoma * Bilirubin ≤ 2 times upper limit of normal * No medical condition that would preclude study treatment * Not pregnant or nursing * Fertile patients must use effective contraception * Shortening fraction ≥ 28% * LVEF ≥ 50% * Glome...
Zoledronic acid is used to treat bone loss and bone complications in conditions including breast cancer, breast cancer with bone metastasis, breast neoplasms, prostate cancer, and osteoporosis. It is also studied in heart transplantation. It is a small molecule bisphosphonate developed by Novartis AG.
Zoledronic acid targets FDPS, also known as farnesyl diphosphate synthase. It acts as an inhibitor of this enzyme, which is involved in the mevalonate pathway. By inhibiting FDPS, zoledronic acid affects osteoclast-mediated bone resorption, which underlies its use in bone loss and cancer-related bone disease.
Zoledronic acid is developed by Novartis AG, which trades under the ticker NVS. Novartis has conducted multiple Phase 3 clinical trials of the drug across bone loss, breast cancer, prostate cancer, and related indications.
Zoledronic acid is in Phase 3 clinical development. It is an investigational small molecule being evaluated in controlled trials. It has completed 11 trials with a total enrollment of 14,788 participants, and one trial remains active.
Zoledronic acid has been studied in trials including NCT01197300, an open-label extension in osteoporotic children on glucocorticoids; NCT00909961, evaluating bone mineral density in postmenopausal osteoporosis; NCT00799266, in osteoporotic children; and NCT00718861, a three-year efficacy and safety study in postmenopausal women with osteoporosis.