Chronic Kidney Disease, Osteoporosis
Conditions
Keywords
Osteoporosis, Osteopenia, Denosumab, Transplantation, Kidney
Brief summary
The primary objective of the study is to examine the effect of denosumab on lumbar spine bone mineral density (BMD) after one year of treatment in newly transplanted renal allograft recipients. Secondary endpoints include BMD changes at the total hip and the femoral neck, changes in body height, changes in bone mineral metabolism parameters, incidence of fractures, and allograft function at one year. Safety measurements include the occurrence of rejection episodes, infectious complications, graft loss and mortality. * Trial with medicinal product
Detailed description
Renal allograft recipients are at high risk to suffer a substantial loss of bone mineral density (BMD) within the first year after kidney transplantation. This loss of BMD correlates with an increased risk for the development of osteoporosis or worsening of pre-existing osteopenia/osteoporosis, heightening the risk for the subsequent occurrence of fractures. Renal allograft recipients are often treated with calcium and vitamin D preparations to prevent BMD loss. The addition of bisphosphonates can further improve BMD. However, bisphosphonates are potentially nephrotoxic and promote adynamic bone disease, and are therefore not regularly prescribed. Receptor Activator of Nuclear factor- Kappa-B Ligand (RANKL) is a key molecule mediating development, activity, and survival of osteoclasts. Osteoporosis results in part from increased osteoclastic bone resorption, and therefore the inhibition of RANKL activity has become an obvious therapeutic strategy to prevent bone mineral density (BMD) loss and the development of osteoporosis. The novel anti-osteoporotic drug denosumab (trade name Prolia®) is a fully human monoclonal antibody against RANKL. By inhibiting the development and the activity as well as reducing the survival of osteoclasts it decreases bone resorption and increases bone density. The hypothesis of the present study is that denosumab has a beneficial effect on the loss of BMD in the first year after renal transplantation. The preservation of BMD is a surrogate parameter, generally predicting subsequent improvements in the occurrence rate of fractures. The hypothesis will be tested by studying the effect of denosumab on BMD in newly transplanted renal allograft recipients. The purpose of the present trial is to study the effect of denosumab on BMD in kidney allograft recipients. The study participants will be treated for 1 year, receiving a total of 2 injections of the standard 60 mg dose at baseline and at 6 months. Ninety sequential renal allograft recipients will be randomized 1:1 to receive two subcutaneous 60 mg denosumab injections within 14 days and 6 months following renal transplantation, or no treatment. All patients will also receive oral standard treatment with 1000 mg calcium plus 800 IU vitamin D.
Interventions
60 mg s.c. injection at baseline and after 6 months
Sponsors
Rudolf Wuethrich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
The key inclusion criteria are: 1. Male or female adult de novo kidney, kidney-pancreas or kidney-islet, or kidney-liver transplant recipients 2. Functioning graft within 28 days after transplantation (creatinine having decreased to \<200 micromol/l without the need for dialysis) 3. Being on standard triple immunosuppression including a calcineurin antagonist (cyclosporine or tacrolimus), mycophenolate (MMF or MPA) and steroids, with or without induction treatment with basiliximab or anti-thymocyte globulin Key
Exclusion criteria
are: 1. Age \<18 years 2. Rising creatinine after initial drop \<200 micromol/l or creatinine \>200 micromol/l at baseline 3. Evidence of early acute rejection, either suspected clinically and/or proven by biopsy 4. Presence of severe osteoporosis as evidenced by a T score \<-4 at the hip, femoral neck or any of the 4 vertebrae L1 to L4 5. Evidence of severe hyper- or hypoparathyroidism (iPTH \>800 ng/l or \<10 ng/l) 6. Hypocalcemia (total calcium \<1.8 mmol/l) or hypercalcemia (total calcium \>2.7 mmol/l) 7. Steroid-free de novo immunosuppression scheme
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 12 | Baseline and month 12 | The total lumbar spine BMD was measured via Dual Energy X-ray Absorptiometry (DXA) and was expressed in g/cm2 hydroxylapatite |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in BMD at the Femoral Neck From Baseline to Month 12 | Baseline and month 12 | The total femoral neck BMD was measured via Dual Energy X-ray Absorptiometry (DXA) and was expressed in g/cm2 hydroxylapatite |
| Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 6 | Baseline and month 6 | The total lumbar spine BMD was measured via DXA and was expressed in g/cm2 hydroxylapatite. |
| Percent Change in BMD at the Total Hip From Baseline to Month 6 | Baseline and month 6 | The total hip BMD was measured via DXA and was expressed in g/cm2 hydroxylapatite |
| Percent Change in BMD at the Total Hip From Baseline to Month 12 | Baseline and month 12 | The total hip BMD was measured via Dual Energy X-ray Absorptiometry (DXA) and was expressed in g/cm2 hydroxylapatite |
| Beta-CTX at Baseline and Months 3, 6 and 12 | baseline, month 3, month 6, and month 12 | Blood concentrations of beta-CTX (microgram/L) |
| P1NP at Baseline and Months 3, 6 and 12 | baseline, month 3, month 6, and month 12 | Blood concentrations of P1NP were measured in microgram/L |
| Percent Change in BMD at the Femoral Neck From Baseline to Month 6 | Baseline and month 6 | The femoral neck BMD was measured via DXA and was expressed in g/cm2 hydroxylapatite |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Cortical Thickness (Ct.Th) at the Distal Tibia | Baseline and month 12 | Cortical thickness was measured via HR-pQCT (Xtreme CT) at the distal tibia and was expressed as mm. |
| Percent Change From Baseline in Total Volumetric Bone Mineral Densitiy (Tot.vBMD) at the Distal Radius | Baseline and month 12 | Volumetric BMD (vBMD) was measured via HR-pQCT (Xtreme CT) at the distal radius and was expressed as mg HA/cm3. |
| 1,25-(OH)2 Vitamin D3 | baseline, months 3, 6, and 12 | Blood levels of 1,25-(OH)2 vitamin D3 were measured as ng/L |
| Percent Change From Baseline in Trabecular Volumetric Bone Mineral Densitiy (Tb.vBMD) at the Distal Radius | Baseline and month 12 | Volumetric BMD (vBMD) was measured via HR-pQCT (Xtreme CT) at the distal radius and was expressed as mg HA/cm3. |
| Percent Change From Baseline in Cortical Thickness (Ct.Th) at the Distal Radius | Baseline and month 12 | Cortical thickness was measured via HR-pQCT (Xtreme CT) at the distal radius and was expressed as mm. |
| Percent Change From Baseline in Cortical Volumetric Bone Mineral Densitiy (Ct.vBMD) at the Distal Radius | Baseline and month 12 | Volumetric BMD (vBMD) was measured via HR-pQCT (Xtreme CT) at the distal radius and was expressed as mg HA/cm3. |
| Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | baseline, months 0.5, 1, 2, 3, 6, 12 | Blood levels of calcium (mmol/L) were measured at baseline and at months 0.5, 1, 2, 3, 6, and 12 |
| Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | baseline, months 0.5, 1, 2, 3, 6, 12 | Blood levels of phosphate (mmol/L) were measured at baseline and at months 0.5, 1, 2, 3, 6, 12 |
| Blood Levels of PTH (ng/L) at Baseline and Months 3, 6, and 12 | baseline and months 3, 6, and 12 | Blood levels of PTH (ng/L) were measured at baseline and at months 3, 6, and 12 |
| 25-OH-vitamin D3 | baseline, months 3, 6, and 12 | Blood levels of 25-OH-vitamin D3 were measured as microgramm/L |
| Percent Change From Baseline in Total Volumetric Bone Mineral Densitiy (Tot.vBMD) at the Distal Tibia | Baseline and month 12 | Volumetric BMD (vBMD) was measured via HR-pQCT (Xtreme CT) at the distal tibia and was expressed as mg HA/cm3. |
| Percent Change From Baseline in Cortical Volumetric Bone Mineral Densitiy (Ct.vBMD) at the Distal Tibia | Baseline and month 12 | Volumetric BMD (vBMD) was measured via HR-pQCT (Xtreme CT) at the distal tibia and was expressed as mg HA/cm3. |
| Percent Change From Baseline in Trabecular Volumetric Bone Mineral Densitiy (Tb.vBMD) at the Distal Tibia | Baseline and month 12 | Volumetric BMD (vBMD) was measured via HR-pQCT (Xtreme CT) at the distal tibia and was expressed as mg HA/cm3. |
Countries
Switzerland
Participant flow
Recruitment details
Patients were recruited from June 20, 2011, to May 2, 2014. Patients were randomized after 15.7 ± 6.4 days after transplantation.
Participants by arm
| Arm | Count |
|---|---|
| Denosumab 60 mg denosumab s.c. at baseline and after 6 months
Denosumab (Prolia): 60 mg s.c. injection at baseline and after 6 months | 46 |
| Control No treatment | 44 |
| Total | 90 |
Baseline characteristics
| Characteristic | Denosumab | Control | Total |
|---|---|---|---|
| Age, Continuous | 48.9 years STANDARD_DEVIATION 16 | 52.9 years STANDARD_DEVIATION 14 | 50.9 years STANDARD_DEVIATION 15.1 |
| Number of osteopenic patients No | 30 participants | 19 participants | 49 participants |
| Number of osteopenic patients Yes | 16 participants | 25 participants | 41 participants |
| Number of osteoporotic patients No | 43 participants | 38 participants | 81 participants |
| Number of osteoporotic patients Yes | 3 participants | 6 participants | 9 participants |
| Region of Enrollment Switzerland | 46 participants | 44 participants | 90 participants |
| Sex: Female, Male Female | 27 Participants | 25 Participants | 52 Participants |
| Sex: Female, Male Male | 19 Participants | 19 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 45 / 46 | 44 / 44 |
| serious Total, serious adverse events | 31 / 46 | 29 / 44 |
Outcome results
Primary
Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 12
The total lumbar spine BMD was measured via Dual Energy X-ray Absorptiometry (DXA) and was expressed in g/cm2 hydroxylapatite
Time frame: Baseline and month 12
Population: The intention-to-treat (ITT) population was used for the primary efficacy analysis, i.e. all subjects were included that have been randomized to the control group or to the denosumab group. Missing values were replaced with a last-value-carried-forward approach (LVCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab | Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 12 | 4.5 percent change | Standard Deviation 3.8 |
| Control | Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 12 | -0.3 percent change | Standard Deviation 5.1 |
Comparison: We calculated that a sample size of 43 patients per group would provide a statistical power of 86% to detect a 4% difference in the percentage change of areal BMD at the total lumbar spine at 12 months, using a two-sided t-test with an α-level of 0.05 and assuming a mean ± SD change of 4 ± 6% in the denosumab group and 0 ± 6% in the control group. To account for a dropout rate of 5%, it was planned to randomize a total of 90 patients.p-value: <0.00195% CI: [3.137, 6.98]ANCOVA
Secondary
Beta-CTX at Baseline and Months 3, 6 and 12
Blood concentrations of beta-CTX (microgram/L)
Time frame: baseline, month 3, month 6, and month 12
Population: For this endpoint, an available case analysis was performed, i.e., all randomised patients with valid data at all time points were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Denosumab | Beta-CTX at Baseline and Months 3, 6 and 12 | baseline | 0.635 microgram/L |
| Denosumab | Beta-CTX at Baseline and Months 3, 6 and 12 | month 3 | 0.129 microgram/L |
| Denosumab | Beta-CTX at Baseline and Months 3, 6 and 12 | month 6 | 0.204 microgram/L |
| Denosumab | Beta-CTX at Baseline and Months 3, 6 and 12 | month 12 | 0.389 microgram/L |
| Control | Beta-CTX at Baseline and Months 3, 6 and 12 | month 12 | 0.794 microgram/L |
| Control | Beta-CTX at Baseline and Months 3, 6 and 12 | baseline | 0.772 microgram/L |
| Control | Beta-CTX at Baseline and Months 3, 6 and 12 | month 6 | 0.612 microgram/L |
| Control | Beta-CTX at Baseline and Months 3, 6 and 12 | month 3 | 0.590 microgram/L |
p-value: <0.001repeated measures GLM
Secondary
P1NP at Baseline and Months 3, 6 and 12
Blood concentrations of P1NP were measured in microgram/L
Time frame: baseline, month 3, month 6, and month 12
Population: For this endpoints, an available case analysis was performed, i.e., all randomised patients with valid data at all time points were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Denosumab | P1NP at Baseline and Months 3, 6 and 12 | baseline | 61.222 microgram/L |
| Denosumab | P1NP at Baseline and Months 3, 6 and 12 | month 6 | 35.347 microgram/L |
| Denosumab | P1NP at Baseline and Months 3, 6 and 12 | month 3 | 40.976 microgram/L |
| Denosumab | P1NP at Baseline and Months 3, 6 and 12 | month 12 | 57.953 microgram/L |
| Control | P1NP at Baseline and Months 3, 6 and 12 | month 3 | 108.699 microgram/L |
| Control | P1NP at Baseline and Months 3, 6 and 12 | baseline | 77.808 microgram/L |
| Control | P1NP at Baseline and Months 3, 6 and 12 | month 12 | 132.439 microgram/L |
| Control | P1NP at Baseline and Months 3, 6 and 12 | month 6 | 107.072 microgram/L |
p-value: <0.001repeated measures GLM
Secondary
Percent Change in BMD at the Femoral Neck From Baseline to Month 12
The total femoral neck BMD was measured via Dual Energy X-ray Absorptiometry (DXA) and was expressed in g/cm2 hydroxylapatite
Time frame: Baseline and month 12
Population: The intention-to-treat (ITT) was used for the analysis of this endpoint, i.e. all subjects were included in the analysis that have been randomized to the control group or to the denosumab group. Missing values were replaced with a last-value-carried-forward approach (LVCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab | Percent Change in BMD at the Femoral Neck From Baseline to Month 12 | 1.1 percent change | Standard Deviation 4.7 |
| Control | Percent Change in BMD at the Femoral Neck From Baseline to Month 12 | 0.8 percent change | Standard Deviation 6 |
p-value: 0.3895% CI: [-1.329, 3.447]ANCOVA
Secondary
Percent Change in BMD at the Femoral Neck From Baseline to Month 6
The femoral neck BMD was measured via DXA and was expressed in g/cm2 hydroxylapatite
Time frame: Baseline and month 6
Population: The intention-to-treat (ITT) population was used for the analysis of this endpoint, i.e. all subjects were included in the analysis that have been randomized to the control group or to the denosumab group. Missing values were replaced with a last-value-carried-forward approach (LVCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab | Percent Change in BMD at the Femoral Neck From Baseline to Month 6 | 1.0 percent change | Standard Deviation 4 |
| Control | Percent Change in BMD at the Femoral Neck From Baseline to Month 6 | -0.8 percent change | Standard Deviation 5.4 |
p-value: 0.06495% CI: [-0.122, 4.193]ANCOVA
Secondary
Percent Change in BMD at the Total Hip From Baseline to Month 12
The total hip BMD was measured via Dual Energy X-ray Absorptiometry (DXA) and was expressed in g/cm2 hydroxylapatite
Time frame: Baseline and month 12
Population: The intention-to-treat (ITT) population was used for the analysis of this endpoint, i.e. all subjects were included in the analysis that have been randomized to the control group or to the denosumab group. Missing values were replaced with a last-value-carried-forward approach (LVCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab | Percent Change in BMD at the Total Hip From Baseline to Month 12 | 2.3 percent change | Standard Deviation 3.7 |
| Control | Percent Change in BMD at the Total Hip From Baseline to Month 12 | 0.5 percent change | Standard Deviation 4.2 |
p-value: 0.03595% CI: [0.132, 3.659]ANCOVA
Secondary
Percent Change in BMD at the Total Hip From Baseline to Month 6
The total hip BMD was measured via DXA and was expressed in g/cm2 hydroxylapatite
Time frame: Baseline and month 6
Population: The intention-to-treat (ITT) population was used for the analysis of this endpoint, i.e. all subjects were included in the analysis that have been randomized to the control group or to the denosumab group. Missing values were replaced with a last-value-carried-forward approach (LVCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab | Percent Change in BMD at the Total Hip From Baseline to Month 6 | 1.4 percent change | Standard Deviation 2.4 |
| Control | Percent Change in BMD at the Total Hip From Baseline to Month 6 | -0.3 percent change | Standard Deviation 1.4 |
p-value: 0.00995% CI: [0.44, 3.072]ANCOVA
Secondary
Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 6
The total lumbar spine BMD was measured via DXA and was expressed in g/cm2 hydroxylapatite.
Time frame: Baseline and month 6
Population: The intention-to-treat was used for the analysis of this endpoint, i.e. all subjects were included in the analysis that have been randomized to the control group or to the denosumab group. Missing values were replaced with a last-value-carried-forward approach (LVCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab | Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 6 | 2.9 percent change | Standard Deviation 3.3 |
| Control | Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 6 | -1.5 percent change | Standard Deviation 4.1 |
p-value: <0.00195% CI: [2.975, 6.178]ANCOVA
Other Pre-specified
1,25-(OH)2 Vitamin D3
Blood levels of 1,25-(OH)2 vitamin D3 were measured as ng/L
Time frame: baseline, months 3, 6, and 12
Population: For this endpoint, an available case analysis was performed, i.e., all randomised patients with valid data at all time points were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Denosumab | 1,25-(OH)2 Vitamin D3 | baseline | 29.556 ng/L |
| Denosumab | 1,25-(OH)2 Vitamin D3 | month 3 | 60.533 ng/L |
| Denosumab | 1,25-(OH)2 Vitamin D3 | month 6 | 54.175 ng/L |
| Denosumab | 1,25-(OH)2 Vitamin D3 | month 12 | 47.208 ng/L |
| Control | 1,25-(OH)2 Vitamin D3 | month 12 | 51.494 ng/L |
| Control | 1,25-(OH)2 Vitamin D3 | baseline | 34.171 ng/L |
| Control | 1,25-(OH)2 Vitamin D3 | month 6 | 58.074 ng/L |
| Control | 1,25-(OH)2 Vitamin D3 | month 3 | 55.276 ng/L |
p-value: 0.607repeated measures GLM
Other Pre-specified
25-OH-vitamin D3
Blood levels of 25-OH-vitamin D3 were measured as microgramm/L
Time frame: baseline, months 3, 6, and 12
Population: For this endpoint, an available case analysis was performed, i.e., all randomised patients with valid data at all time points were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Denosumab | 25-OH-vitamin D3 | baseline | 17.378 microgramm/L |
| Denosumab | 25-OH-vitamin D3 | month 3 | 21.632 microgramm/L |
| Denosumab | 25-OH-vitamin D3 | month 6 | 24.395 microgramm/L |
| Denosumab | 25-OH-vitamin D3 | month 12 | 28.546 microgramm/L |
| Control | 25-OH-vitamin D3 | month 12 | 28.358 microgramm/L |
| Control | 25-OH-vitamin D3 | baseline | 18.058 microgramm/L |
| Control | 25-OH-vitamin D3 | month 6 | 26.728 microgramm/L |
| Control | 25-OH-vitamin D3 | month 3 | 22.903 microgramm/L |
p-value: 0.578repeated measures GLM
Other Pre-specified
Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12
Blood levels of calcium (mmol/L) were measured at baseline and at months 0.5, 1, 2, 3, 6, and 12
Time frame: baseline, months 0.5, 1, 2, 3, 6, 12
Population: For this endpoints, an available case analysis was performed, thus all randomised patients with valid data at all time points were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Denosumab | Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 1 | 2.293 mmol/L |
| Denosumab | Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 3 | 2.404 mmol/L |
| Denosumab | Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 0.5 | 2.131 mmol/L |
| Denosumab | Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 6 | 2.463 mmol/L |
| Denosumab | Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 2 | 2.420 mmol/L |
| Denosumab | Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 12 | 2.480 mmol/L |
| Denosumab | Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | baseline | 2.320 mmol/L |
| Control | Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 12 | 2.509 mmol/L |
| Control | Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | baseline | 2.317 mmol/L |
| Control | Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 0.5 | 2.405 mmol/L |
| Control | Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 1 | 2.444 mmol/L |
| Control | Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 2 | 2.480 mmol/L |
| Control | Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 3 | 2.461 mmol/L |
| Control | Blood Levels of Calcium (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 6 | 2.453 mmol/L |
p-value: 0.014repeated measures GLM
Other Pre-specified
Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12
Blood levels of phosphate (mmol/L) were measured at baseline and at months 0.5, 1, 2, 3, 6, 12
Time frame: baseline, months 0.5, 1, 2, 3, 6, 12
Population: For this endpoints, an available case analysis was performed, i.e., all randomised patients with valid data at all time points were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Denosumab | Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 1 | 0.605 mmol/L |
| Denosumab | Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 3 | 0.742 mmol/L |
| Denosumab | Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 0.5 | 0.525 mmol/L |
| Denosumab | Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 6 | 0.804 mmol/L |
| Denosumab | Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 2 | 0.726 mmol/L |
| Denosumab | Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 12 | 0.842 mmol/L |
| Denosumab | Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | baseline | 0.582 mmol/L |
| Control | Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 12 | 0.902 mmol/L |
| Control | Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | baseline | 0.586 mmol/L |
| Control | Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 0.5 | 0.714 mmol/L |
| Control | Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 1 | 0.726 mmol/L |
| Control | Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 2 | 0.812 mmol/L |
| Control | Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 3 | 0.776 mmol/L |
| Control | Blood Levels of Phosphate (mmol/L) at Baseline and Months 0.5, 1, 2, 3, 6, 12 | month 6 | 0.849 mmol/L |
p-value: 0.068repeated measures GLM
Other Pre-specified
Blood Levels of PTH (ng/L) at Baseline and Months 3, 6, and 12
Blood levels of PTH (ng/L) were measured at baseline and at months 3, 6, and 12
Time frame: baseline and months 3, 6, and 12
Population: For this endpoint, an available case analysis was performed, i.e., all randomised patients with valid data at all time points were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Denosumab | Blood Levels of PTH (ng/L) at Baseline and Months 3, 6, and 12 | baseline | 163.110 ng/L |
| Denosumab | Blood Levels of PTH (ng/L) at Baseline and Months 3, 6, and 12 | month 3 | 173.573 ng/L |
| Denosumab | Blood Levels of PTH (ng/L) at Baseline and Months 3, 6, and 12 | month 6 | 157.043 ng/L |
| Denosumab | Blood Levels of PTH (ng/L) at Baseline and Months 3, 6, and 12 | month 12 | 106.650 ng/L |
| Control | Blood Levels of PTH (ng/L) at Baseline and Months 3, 6, and 12 | month 12 | 100.705 ng/L |
| Control | Blood Levels of PTH (ng/L) at Baseline and Months 3, 6, and 12 | baseline | 147.300 ng/L |
| Control | Blood Levels of PTH (ng/L) at Baseline and Months 3, 6, and 12 | month 6 | 99.420 ng/L |
| Control | Blood Levels of PTH (ng/L) at Baseline and Months 3, 6, and 12 | month 3 | 111.563 ng/L |
p-value: 0.114repeated measures GLM
Other Pre-specified
Percent Change From Baseline in Cortical Thickness (Ct.Th) at the Distal Radius
Cortical thickness was measured via HR-pQCT (Xtreme CT) at the distal radius and was expressed as mm.
Time frame: Baseline and month 12
Population: Subgroup of patients (n=24) who participated in the HR-pQCT (Xtreme CT) subprotocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab | Percent Change From Baseline in Cortical Thickness (Ct.Th) at the Distal Radius | 0.9 Percent change |
| Control | Percent Change From Baseline in Cortical Thickness (Ct.Th) at the Distal Radius | -3.6 Percent change |
p-value: 0.048Wilcoxon (Mann-Whitney)
Other Pre-specified
Percent Change From Baseline in Cortical Thickness (Ct.Th) at the Distal Tibia
Cortical thickness was measured via HR-pQCT (Xtreme CT) at the distal tibia and was expressed as mm.
Time frame: Baseline and month 12
Population: Subgroup of patients (n=24) who participated in the HR-pQCT (Xtreme CT) subprotocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab | Percent Change From Baseline in Cortical Thickness (Ct.Th) at the Distal Tibia | 2.8 Percent change |
| Control | Percent Change From Baseline in Cortical Thickness (Ct.Th) at the Distal Tibia | -0.9 Percent change |
p-value: 0.005Wilcoxon (Mann-Whitney)
Other Pre-specified
Percent Change From Baseline in Cortical Volumetric Bone Mineral Densitiy (Ct.vBMD) at the Distal Radius
Volumetric BMD (vBMD) was measured via HR-pQCT (Xtreme CT) at the distal radius and was expressed as mg HA/cm3.
Time frame: Baseline and month 12
Population: Subgroup of patients (n=24) who participated in the HR-pQCT (Xtreme CT) subprotocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab | Percent Change From Baseline in Cortical Volumetric Bone Mineral Densitiy (Ct.vBMD) at the Distal Radius | -0.1 Percent change |
| Control | Percent Change From Baseline in Cortical Volumetric Bone Mineral Densitiy (Ct.vBMD) at the Distal Radius | -0.9 Percent change |
p-value: 0.212Wilcoxon (Mann-Whitney)
Other Pre-specified
Percent Change From Baseline in Cortical Volumetric Bone Mineral Densitiy (Ct.vBMD) at the Distal Tibia
Volumetric BMD (vBMD) was measured via HR-pQCT (Xtreme CT) at the distal tibia and was expressed as mg HA/cm3.
Time frame: Baseline and month 12
Population: Subgroup of patients (n=24) who participated in the HR-pQCT (Xtreme CT) subprotocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab | Percent Change From Baseline in Cortical Volumetric Bone Mineral Densitiy (Ct.vBMD) at the Distal Tibia | 0.1 Percent change |
| Control | Percent Change From Baseline in Cortical Volumetric Bone Mineral Densitiy (Ct.vBMD) at the Distal Tibia | -0.5 Percent change |
p-value: 0.042Wilcoxon (Mann-Whitney)
Other Pre-specified
Percent Change From Baseline in Total Volumetric Bone Mineral Densitiy (Tot.vBMD) at the Distal Radius
Volumetric BMD (vBMD) was measured via HR-pQCT (Xtreme CT) at the distal radius and was expressed as mg HA/cm3.
Time frame: Baseline and month 12
Population: Subgroup of patients (n=24) who participated in the HR-pQCT (Xtreme CT) subprotocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab | Percent Change From Baseline in Total Volumetric Bone Mineral Densitiy (Tot.vBMD) at the Distal Radius | 1.3 Percent change |
| Control | Percent Change From Baseline in Total Volumetric Bone Mineral Densitiy (Tot.vBMD) at the Distal Radius | -1.6 Percent change |
p-value: 0.031Wilcoxon (Mann-Whitney)
Other Pre-specified
Percent Change From Baseline in Total Volumetric Bone Mineral Densitiy (Tot.vBMD) at the Distal Tibia
Volumetric BMD (vBMD) was measured via HR-pQCT (Xtreme CT) at the distal tibia and was expressed as mg HA/cm3.
Time frame: Baseline and month 12
Population: Subgroup of patients (n=24) who participated in the HR-pQCT (Xtreme CT) subprotocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab | Percent Change From Baseline in Total Volumetric Bone Mineral Densitiy (Tot.vBMD) at the Distal Tibia | 2.2 Percent change |
| Control | Percent Change From Baseline in Total Volumetric Bone Mineral Densitiy (Tot.vBMD) at the Distal Tibia | -0.3 Percent change |
p-value: 0.019Wilcoxon (Mann-Whitney)
Other Pre-specified
Percent Change From Baseline in Trabecular Volumetric Bone Mineral Densitiy (Tb.vBMD) at the Distal Radius
Volumetric BMD (vBMD) was measured via HR-pQCT (Xtreme CT) at the distal radius and was expressed as mg HA/cm3.
Time frame: Baseline and month 12
Population: Subgroup of patients (n=24) who participated in the HR-pQCT (Xtreme CT) subprotocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab | Percent Change From Baseline in Trabecular Volumetric Bone Mineral Densitiy (Tb.vBMD) at the Distal Radius | 2.4 Percent change |
| Control | Percent Change From Baseline in Trabecular Volumetric Bone Mineral Densitiy (Tb.vBMD) at the Distal Radius | 0.2 Percent change |
p-value: 0.108Wilcoxon (Mann-Whitney)
Other Pre-specified
Percent Change From Baseline in Trabecular Volumetric Bone Mineral Densitiy (Tb.vBMD) at the Distal Tibia
Volumetric BMD (vBMD) was measured via HR-pQCT (Xtreme CT) at the distal tibia and was expressed as mg HA/cm3.
Time frame: Baseline and month 12
Population: Subgroup of patients (n=24) who participated in the HR-pQCT (Xtreme CT) subprotocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab | Percent Change From Baseline in Trabecular Volumetric Bone Mineral Densitiy (Tb.vBMD) at the Distal Tibia | 1.8 Percent change |
| Control | Percent Change From Baseline in Trabecular Volumetric Bone Mineral Densitiy (Tb.vBMD) at the Distal Tibia | 1.1 Percent change |
p-value: 0.371Wilcoxon (Mann-Whitney)