IOP, Osteoporosis
Conditions
Keywords
premenopausal women
Brief summary
The primary goal of the study is to assess the extent to which bisphosphonate therapy will prevent decreases in bone mass that may occur after cessation of denosumab in premenopausal women with idiopathic osteoporosis (IOP) enrolled in AAAN0161 (FD05114) Denosumab for the prevention of post-teriparatide bone loss in premenopausal women with idiopathic osteoporosis. In addition, the investigator will observe participants for a second year off bisphosphonate therapy to assess duration of response. The hypothesis is that bisphosphonate therapy with alendronate or zoledronic acid, initiated after recovery of bone remodeling activity, will prevent significant bone loss after discontinuing denosumab.
Detailed description
Osteoporosis in premenopausal women with normal menstrual function and no specific cause is termed idiopathic osteoporosis (IOP). IOP is a rare disease with an estimated prevalence of \<200,000 affected premenopausal women in the United States. Women with IOP completing at least one year and up to three years of denosumab (Protocol AAAN0161) will be offered participation in this open-label study in which they would choose whether to take oral alendronate 70 mg weekly for 12 months or a single intravenous dose of zoledronic acid 5 mg. Subjects and study personnel will be blinded to BMD outcomes until 12 months. Discontinuation of denosumab is followed by substantial increases in bone turnover markers to well above baseline, bone resorption reaching twice baseline levels for about 6 months. Over the first 12 months off therapy, all the bone density gained on treatment is lost. Studies done at the institution has demonstrated the occurrence of multiple vertebral fractures in some patients who have stopped denosumab. Based upon these new fracture data, the Prolia label is currently recommending that consideration should be given to transition to another antiresorptive drug in patients stopping denosumab. The main goals of this extension study are to determine rates of bone loss and incidence of radiographic vertebral fractures during one year of bisphosphonate therapy (oral alendronate or intravenous zoledronic acid) initiated after completing denosumab.
Interventions
DRUGAlendronate
oral alendronate 70 mg weekly for 12 months will be given for the prevention of osteoporosis
DRUGZoledronic Acid
single intravenous dose of zoledronic acid 5 mg will be given for the prevention of osteoporosis
Sponsors
Amgen
Columbia University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
open-label study in which they would choose whether to take oral alendronate 70 mg weekly for 12 months or a single intravenous dose of zoledronic acid 5 mg.
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* All women completing at least 12 months of Forteo treatment and at least 12 months of denosumab under previous research studies who remain without a diagnosis of an excluded medical condition and medication exposures as detailed below, will be offered enrollment into this study.
Exclusion criteria
* Known intolerance to calcium supplements * Contraindications to bisphosphonate treatment: 1. Hypocalcemia 2. Pregnancy 3. Known hypersensitivity to bisphosphonates * History of osteomalacia * History of osteonecrosis of the jaw * History of dental extraction or other invasive dental surgery within the prior 4 weeks * Invasive dental work planned in the next 12 months * Any condition or illness (acute, chronic, or history), which in the opinion of the Investigator might interfere with the evaluation of efficacy and safety during the study or may otherwise compromise the safety of the subject * Self-reported or known alcohol or drug abuse within the previous 12 months * Current or recent (within 1 year of enrollment) inflammatory bowel disease or malabsorption * Abnormal laboratory tests performed during Visit 1 1. Renal insufficiency or liver disease: estimated glomerular filtration rate (eGFR) \< 35 ml/min, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \>50% above upper limit of normal 2. Hypercalcemia, hypocalcemia 3. Vitamin D deficiency: 25-Hydroxyvitamin D (25-OHD) \< 30 ng/mL * Subjects must be willing to participate voluntarily. Specifically excluded are the following: 1) women less than 20 (or 35 in the case of those who wish to participate because they have low BMD); 2) protected individuals (institutionalized); 3) prisoners; 4) any other prospective participant who, for any reason, might not be able to give voluntary informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in BMD at the Lumbar Spine (L1-4) Within Group | Baseline, 12 month | Within-group difference (percent change) in BMD at the lumbar spine (L1-4) will be measured by Dual-energy X-ray absorptiometry (DXA) and calculated. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alendronate Subjects will receive oral alendronate
Alendronate: oral alendronate 70 mg weekly for 12 months will be given for the prevention of osteoporosis | 18 |
| Zoledronic Acid Subjects will receive zoledronic acid
Zoledronic Acid: single intravenous dose of zoledronic acid 5 mg will be given for the prevention of osteoporosis | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | Zoledronic Acid | Total | Alendronate |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 24 Participants | 18 Participants |
| Age, Continuous | 34.7 years STANDARD_DEVIATION 6.3 | 37.7 years STANDARD_DEVIATION 8.1 | 38.7 years STANDARD_DEVIATION 8.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 24 Participants | 18 Participants |
| Region of Enrollment United States | 6 participants | 24 participants | 18 participants |
| Sex: Female, Male Female | 6 Participants | 24 Participants | 18 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 6 |
| other Total, other adverse events | 12 / 18 | 6 / 6 |
| serious Total, serious adverse events | 0 / 18 | 0 / 6 |
Outcome results
Primary
Difference in BMD at the Lumbar Spine (L1-4) Within Group
Within-group difference (percent change) in BMD at the lumbar spine (L1-4) will be measured by Dual-energy X-ray absorptiometry (DXA) and calculated.
Time frame: Baseline, 12 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alendronate | Difference in BMD at the Lumbar Spine (L1-4) Within Group | -1.1 percentage of change | Standard Deviation 4.8 |
| Zoledronic Acid | Difference in BMD at the Lumbar Spine (L1-4) Within Group | -2.4 percentage of change | Standard Deviation 1 |