Trial Outcomes & Findings for Bone Modeling Effects of Combined Anabolic/Antiresorptive Administration (NCT NCT04026256)

Last Updated: 2023-08-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

37 participants

Primary outcome timeframe

3 months after first dose of study drug

Results posted on

2023-08-02

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Teriparatide Only daily subcutaneous injection teriparatide for 3 months Teriparatide: teriparatide daily subcutaneous injection	Denosumab Only one dose of subcutaneous injection denosumab Denosumab: denosumab subcutaneous injection	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
Overall Study STARTED	13	9	12
Overall Study COMPLETED	10	8	9
Overall Study NOT COMPLETED	3	1	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bone Modeling Effects of Combined Anabolic/Antiresorptive Administration

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Teriparatide Only n=13 Participants daily subcutaneous injection teriparatide for 3 months Teriparatide: teriparatide daily subcutaneous injection	Denosumab Only n=9 Participants one dose of subcutaneous injection denosumab Denosumab: denosumab subcutaneous injection	Denosumab and Teriparatide n=12 Participants daily subcutaneous injection teriparatide for 3 months plus one dose of subcutaneous injection denosumab Teriparatide: teriparatide daily subcutaneous injection Denosumab: denosumab subcutaneous injection	Total n=34 Participants Total of all reporting groups
Age, Continuous	66 years n=5 Participants	64 years n=7 Participants	65 years n=5 Participants	66 years n=4 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants	34 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants	31 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	26 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Lumbar Spine bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) (g/cm2)	0.87 g/cm2 STANDARD_DEVIATION 0.09 • n=5 Participants	0.80 g/cm2 STANDARD_DEVIATION 0.09 • n=7 Participants	0.81 g/cm2 STANDARD_DEVIATION 0.06 • n=5 Participants	0.83 g/cm2 STANDARD_DEVIATION 0.08 • n=4 Participants
Femoral Neck BMD by DXA (g/cm2)	0.62 g/cm2 STANDARD_DEVIATION 0.07 • n=5 Participants	0.64 g/cm2 STANDARD_DEVIATION 0.06 • n=7 Participants	0.60 g/cm2 STANDARD_DEVIATION 0.08 • n=5 Participants	0.62 g/cm2 STANDARD_DEVIATION 0.07 • n=4 Participants
Total Hip BMD by DXA (g/cm2)	0.75 g/cm2 STANDARD_DEVIATION 0.11 • n=5 Participants	0.73 g/cm2 STANDARD_DEVIATION 0.08 • n=7 Participants	0.72 g/cm2 STANDARD_DEVIATION 0.10 • n=5 Participants	0.74 g/cm2 STANDARD_DEVIATION 0.10 • n=4 Participants

PRIMARY outcome

Timeframe: 3 months after first dose of study drug

Population: refers to number of subjects who had bone biopsies available for analysis.

Outcome measures

Outcome measures
Measure	Teriparatide Only n=9 Participants daily subcutaneous injection teriparatide for 3 months Teriparatide: teriparatide daily subcutaneous injection	Denosumab Only n=8 Participants one dose of subcutaneous injection denosumab Denosumab: denosumab subcutaneous injection	Denosumab and Teriparatide n=9 Participants daily subcutaneous injection teriparatide for 3 months plus one dose of subcutaneous injection denosumab Teriparatide: teriparatide daily subcutaneous injection Denosumab: denosumab subcutaneous injection
Cancellous Bone Formation Rate at Month 3	0.13 mm3/mm2/day Standard Deviation 0.06	0.01 mm3/mm2/day Standard Deviation 0.01	0.06 mm3/mm2/day Standard Deviation 0.02

Adverse Events

Teriparatide Only

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Denosumab Only

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Denosumab and Teriparatide

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Teriparatide Only n=13 participants at risk daily subcutaneous injection teriparatide for 3 months Teriparatide: teriparatide daily subcutaneous injection	Denosumab Only n=9 participants at risk one dose of subcutaneous injection denosumab Denosumab: denosumab subcutaneous injection	Denosumab and Teriparatide n=12 participants at risk daily subcutaneous injection teriparatide for 3 months plus one dose of subcutaneous injection denosumab Teriparatide: teriparatide daily subcutaneous injection Denosumab: denosumab subcutaneous injection
Skin and subcutaneous tissue disorders phototoxic dermatitis	7.7% 1/13 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	0.00% 0/9 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	0.00% 0/12 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).
Cardiac disorders transient syncopal event	0.00% 0/13 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	0.00% 0/9 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	8.3% 1/12 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).

Other adverse events

Other adverse events
Measure	Teriparatide Only n=13 participants at risk daily subcutaneous injection teriparatide for 3 months Teriparatide: teriparatide daily subcutaneous injection	Denosumab Only n=9 participants at risk one dose of subcutaneous injection denosumab Denosumab: denosumab subcutaneous injection	Denosumab and Teriparatide n=12 participants at risk daily subcutaneous injection teriparatide for 3 months plus one dose of subcutaneous injection denosumab Teriparatide: teriparatide daily subcutaneous injection Denosumab: denosumab subcutaneous injection
Ear and labyrinth disorders rhinorrhea	15.4% 2/13 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	11.1% 1/9 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	16.7% 2/12 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).
Gastrointestinal disorders nausea	30.8% 4/13 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	22.2% 2/9 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	33.3% 4/12 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).
Musculoskeletal and connective tissue disorders joint pain	0.00% 0/13 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	44.4% 4/9 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	16.7% 2/12 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).
Musculoskeletal and connective tissue disorders myalgia	0.00% 0/13 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	0.00% 0/9 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	16.7% 2/12 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).
Musculoskeletal and connective tissue disorders propagation of fracture at biopsy site	0.00% 0/13 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	22.2% 2/9 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	0.00% 0/12 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).
Nervous system disorders dizziness	7.7% 1/13 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	11.1% 1/9 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	16.7% 2/12 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).
Nervous system disorders headache	15.4% 2/13 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	0.00% 0/9 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	33.3% 4/12 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).
Skin and subcutaneous tissue disorders pruritus	0.00% 0/13 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	0.00% 0/9 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	16.7% 2/12 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).
General disorders fatigue	0.00% 0/13 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	0.00% 0/9 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).	25.0% 3/12 • adverse event data was collected from baseline to approximately 1 month after study completion, for an average duration of 5 months per participant (assuming that the participant completed the whole study).

Additional Information

Benjamin Leder

Massachusetts General Hospital

Phone: 617-724-2039

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place