Postmenopausal Osteoporosis
Conditions
Keywords
osteoporosis, histomorphometry, bone density, teriparatide, denosumab
Brief summary
The purpose of this study is to examine, via iliac crest bone biopsies, the mechanism of combined teriparatide and denosumab on the bone of postmenopausal osteoporotic women after 3 months of treatment.
Interventions
DRUGTeriparatide
teriparatide daily subcutaneous injection
DRUGDenosumab
denosumab subcutaneous injection
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* women aged 45+ * postmenopausal * osteoporotic with high risk of fracture
Exclusion criteria
* significant previous use of bone health modifying treatments * known congenital or acquired bone disease other than osteoporosis * significant renal disease, liver disease, cardiopulmonary disease, or psychiatric disease * abnormal calcium or parathyroid hormone level * serum vitamin D \<20 ng/mL or \>60ng/mL * serum alkaline phosphatase above upper normal limit with no explanation * anemia (hematocrit \<32%) * history of malignancy (except non-melanoma skin carcinoma), radiation therapy, or gouty arthritis * history of urolithiasis within the last one year * excessive alcohol use or substance abuse * use of oral or parenteral glucocorticoids for more than 14 days within the past 6 months * extensive dental work involving extraction or dental implant within the past or upcoming 2 months * known sensitivity to mammalian cell-derived drug products * known contraindications to denosumab, teriparatide, or any of their excipients * known contraindications to tetracycline, demeclocycline, or other antibiotics in this drug class * continuous use of tetracycline for \>1-month duration within the last 10 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cancellous Bone Formation Rate at Month 3 | 3 months after first dose of study drug | Cancellous bone formation rate at month 3 is calculated from the cancellous (trabecular) compartment of the iliac crest bone biopsy specimens. Bone formation rate (BFR/BS, mm3/mm2/day): amount of new bone formed in unit time per unit of bone surface. It is calculated by multiplying the mineralizing surface/bone surface (MS/BS) by the mineral apposition rate (MAR) - see below for how MS/BS and MAR are calculated. Mineralizing surface (MS/BS, %): is the percent of bone surface that displays a tetracycline label reflecting active mineralization. It is calculated as the double-labeled surface plus one half of the single-labeled surface and is expressed as a function of total bone surface. It is a measure of the proportion of bone surface upon which new mineralized bone was being deposited during the period of tetracycline labeling. Mineral apposition rate (MAR mm/day): is the mean distance between the double labels, divided by the time interval between them. |
Countries
United States
Participant flow
Pre-assignment details
37 participants enrolled in the study. 3 participants withdrew their consent very soon after signing the consent form and PRIOR to randomization to a treatment arm. Thus we are reporting this as 37 enrolled in the study and 34 enrolled AND randomized.
Participants by arm
| Arm | Count |
|---|---|
| Teriparatide Only daily subcutaneous injection teriparatide for 3 months
Teriparatide: teriparatide daily subcutaneous injection | 13 |
| Denosumab Only one dose of subcutaneous injection denosumab
Denosumab: denosumab subcutaneous injection | 9 |
| Denosumab and Teriparatide daily subcutaneous injection teriparatide for 3 months plus one dose of subcutaneous injection denosumab
Teriparatide: teriparatide daily subcutaneous injection
Denosumab: denosumab subcutaneous injection | 12 |
| Total | 34 |
Baseline characteristics
| Characteristic | Teriparatide Only | Denosumab Only | Denosumab and Teriparatide | Total |
|---|---|---|---|---|
| Age, Continuous | 66 years | 64 years | 65 years | 66 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 8 Participants | 11 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Femoral Neck BMD by DXA (g/cm2) | 0.62 g/cm2 STANDARD_DEVIATION 0.07 | 0.64 g/cm2 STANDARD_DEVIATION 0.06 | 0.60 g/cm2 STANDARD_DEVIATION 0.08 | 0.62 g/cm2 STANDARD_DEVIATION 0.07 |
| Lumbar Spine bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) (g/cm2) | 0.87 g/cm2 STANDARD_DEVIATION 0.09 | 0.80 g/cm2 STANDARD_DEVIATION 0.09 | 0.81 g/cm2 STANDARD_DEVIATION 0.06 | 0.83 g/cm2 STANDARD_DEVIATION 0.08 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 8 Participants | 8 Participants | 26 Participants |
| Sex: Female, Male Female | 13 Participants | 9 Participants | 12 Participants | 34 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Total Hip BMD by DXA (g/cm2) | 0.75 g/cm2 STANDARD_DEVIATION 0.11 | 0.73 g/cm2 STANDARD_DEVIATION 0.08 | 0.72 g/cm2 STANDARD_DEVIATION 0.1 | 0.74 g/cm2 STANDARD_DEVIATION 0.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 9 | 0 / 12 |
| other Total, other adverse events | 5 / 13 | 6 / 9 | 9 / 12 |
| serious Total, serious adverse events | 1 / 13 | 0 / 9 | 1 / 12 |
Outcome results
Primary
Cancellous Bone Formation Rate at Month 3
Cancellous bone formation rate at month 3 is calculated from the cancellous (trabecular) compartment of the iliac crest bone biopsy specimens. Bone formation rate (BFR/BS, mm3/mm2/day): amount of new bone formed in unit time per unit of bone surface. It is calculated by multiplying the mineralizing surface/bone surface (MS/BS) by the mineral apposition rate (MAR) - see below for how MS/BS and MAR are calculated. Mineralizing surface (MS/BS, %): is the percent of bone surface that displays a tetracycline label reflecting active mineralization. It is calculated as the double-labeled surface plus one half of the single-labeled surface and is expressed as a function of total bone surface. It is a measure of the proportion of bone surface upon which new mineralized bone was being deposited during the period of tetracycline labeling. Mineral apposition rate (MAR mm/day): is the mean distance between the double labels, divided by the time interval between them.
Time frame: 3 months after first dose of study drug
Population: refers to number of subjects who had bone biopsies available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriparatide Only | Cancellous Bone Formation Rate at Month 3 | 0.13 mm3/mm2/day | Standard Deviation 0.06 |
| Denosumab Only | Cancellous Bone Formation Rate at Month 3 | 0.01 mm3/mm2/day | Standard Deviation 0.01 |
| Denosumab and Teriparatide | Cancellous Bone Formation Rate at Month 3 | 0.06 mm3/mm2/day | Standard Deviation 0.02 |