Differentiated Thyroid Cancer, Osteoporosis
Conditions
Keywords
differentiated thyroid cancer, bone mineral density, thyroid stimulating hormone suppression
Brief summary
Postmenopausal women with differentiated thyroid cancer (DTC) taking suppressive doses of levothyroxine (L-T4) are thought to have accelerated bone loss and increased risk of osteoporosis. Therefore, the investigators try to investigate the effects of 99Tc-MDP,alendronate sodium in postmenopausal women with DTC under TSH suppression and osteoporosis.
Detailed description
Differentiated thyroid cancer (DTC) has become one of the most common endocrine malignancies. According to American Thyroid Association (ATA) and Chinese Thyroid Association (CTA), most of DTC patients undergo total or near total thyroidectomy, radioiodine ablation and TSH (thyroid stimulating hormone) suppression. Osteoporosis (OS) and fractures are important comorbidities in patients with DTC, with potential negative impact on quality of life (QOL) and survival. The main determinant of skeletal fragility in DTC is the TSH suppression. Postmenopausal women with DTC under TSH suppression therapy are more vulnerable to OS. Technetium-99 methylene diphosphonate (99Tc-MDP) is a decay product of 99mTc-MDP (used for bone scintigraphy) and a novel bisphosphonates, which has been used in China for diseases like rheumatoid arthritis (RA), ankylosing spondylitis (AS) and osteochondral lesions of the talus, etc. However, as a member of bisphosphates, little attention has been paid to its anti-OS effect for DTC under TSH suppression.
Sponsors
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients with OS were divided into 99Tc-MDP and fosamax treatment groups.
Eligibility
Sex/Gender
FEMALE
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(1) They were pathologically diagnosed with DTC including papillary or follicular carcinoma. (2) They received a near total thyroidectomy and radioiodine treatment. (3) TSH suppression should be at least one year before the study. (4) Bone mineral density (BMD) in lumbar spine and/or hip was tested by Dual-energy X-ray absorptiometry (DXA) at baseline, 6 month (m) and/or 12m follow up. 5) The diagnosis of osteoporosis was T-score ≤-2.5 SD at the lumbar spine, or hip.
Exclusion criteria
1. patients having medications for osteoporosis before TSH suppression treatment; 2. secondary osteoporosis ; 3. severe liver or kidney disease; 4. myelosuppression; 5. digestive disease; 6. long term use of immunosuppressive agent, estrogen or estrogen receptor modulators. This study was approved by the Institutional Review Board of Hospital Research Ethics. All the patients were fully acquainted with their treatment and consented to participate in the clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change of Bone Mineral Density in Lumbar and Hip | baseline, 6 months, and 12 months | Percent change of bone mineral density in lumbar and hip by dual energy x-ray absorptiometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bone Turnover Markers | baseline and 12 months | bone turnover markers including C-telopeptides of type I collagen (CTX), Type I N-procollagen terminal propeptide(PINP) |
| Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | baseline, 6 months, and 12 months | The health related quality of life was measured by 36-item Short Form Health Status Survey questionnaire (SF-36). The minimum and maximum values were 0 and 100, respectively. Higher scores mean a better a better outcome. The questionnaire includes 36 items that can be classified into the following eight health status subscales: Physical Functioning, Physical Role Limitations, Bodily Pain, General Health Perception, Vitality, Social Functioning, Emotional Role Limitations, and Mental Health. A standardized Physical Component Summary and a standardized mental component score were calculated. The physical component summary and mental component summary represent the deviation from the reference population in Sweden. Higher scores mean a better a better outcome. |
| Side Effects | 6 months, and 12 months | A transient rash and phlebitis, gastrointestinal reaction. |
Countries
China
Participant flow
Recruitment details
Patients were enrolled in three centers (Tenth People's Hospital of Tongji University, Shanghai No. 4 People's Hospital and Xinhua Hospital School of Medicine Shanghai Jiaotong University) from January 2015 to December 2019.
Pre-assignment details
In the total of 142 included patients, 70 were treated with 99Tc-MDP and 72 were treated with Fosamax.
Participants by arm
| Arm | Count |
|---|---|
| 99Tc-MDP 15mg 99Tc-MDP were intravenously administered twice a week for 10 weeks, then once a week for 8 weeks, every two weeks for 22 weeks and monthly for another 3m.
99Tc-MDP: 99Tc-MDP, H20000218 | 70 |
| Fosamax 70mg po every week for 12 months.
Alendronate Sodium: H20080172 | 72 |
| Total | 142 |
Baseline characteristics
| Characteristic | Fosamax | Total | 99Tc-MDP |
|---|---|---|---|
| Age, Continuous | 62.73 years STANDARD_DEVIATION 7.24 | 63 years STANDARD_DEVIATION 7 | 64.29 years STANDARD_DEVIATION 7.96 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment China | 72 participants | 142 participants | 70 participants |
| Sex/Gender, Customized Sex: Female | 72 participants | 142 participants | 70 participants |
| TNM staging T1-2Nx | 2 number of participants | 3 number of participants | 1 number of participants |
| TNM staging T1N0-1 | 39 number of participants | 74 number of participants | 35 number of participants |
| TNM staging T2N0-1 | 5 number of participants | 11 number of participants | 6 number of participants |
| TNM staging T3N0-1 | 9 number of participants | 13 number of participants | 4 number of participants |
| TNM staging T4N0-1 | 12 number of participants | 30 number of participants | 18 number of participants |
| TNM staging TxN0-1 | 4 number of participants | 9 number of participants | 5 number of participants |
| TNM staging TxNx | 1 number of participants | 2 number of participants | 1 number of participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 72 |
| other Total, other adverse events | 0 / 70 | 6 / 72 |
| serious Total, serious adverse events | 0 / 70 | 0 / 72 |
Outcome results
Primary
Percent Change of Bone Mineral Density in Lumbar and Hip
Percent change of bone mineral density in lumbar and hip by dual energy x-ray absorptiometry
Time frame: baseline, 6 months, and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 99Tc-MDP | Percent Change of Bone Mineral Density in Lumbar and Hip | Percentage change of lumbar spine at month 6 | 3.0 percentage change | Standard Deviation 6.6 |
| 99Tc-MDP | Percent Change of Bone Mineral Density in Lumbar and Hip | Percentage change of total hip at month 6 | 0.9 percentage change | Standard Deviation 7.7 |
| 99Tc-MDP | Percent Change of Bone Mineral Density in Lumbar and Hip | Percentage change of lumbar spine month 12 | 3.8 percentage change | Standard Deviation 10.9 |
| 99Tc-MDP | Percent Change of Bone Mineral Density in Lumbar and Hip | Percentage change of total hip at month 12 | 5.1 percentage change | Standard Deviation 17 |
| Fosamax | Percent Change of Bone Mineral Density in Lumbar and Hip | Percentage change of lumbar spine month 12 | 5.1 percentage change | Standard Deviation 6.1 |
| Fosamax | Percent Change of Bone Mineral Density in Lumbar and Hip | Percentage change of lumbar spine at month 6 | 3.2 percentage change | Standard Deviation 7.1 |
| Fosamax | Percent Change of Bone Mineral Density in Lumbar and Hip | Percentage change of total hip at month 12 | 4.6 percentage change | Standard Deviation 9.6 |
| Fosamax | Percent Change of Bone Mineral Density in Lumbar and Hip | Percentage change of total hip at month 6 | 4.9 percentage change | Standard Deviation 7.7 |
Secondary
Bone Turnover Markers
bone turnover markers including C-telopeptides of type I collagen (CTX), Type I N-procollagen terminal propeptide(PINP)
Time frame: baseline and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 99Tc-MDP | Bone Turnover Markers | PINP before treatment | 43.7725 ng/ml | Standard Deviation 14.74802 |
| 99Tc-MDP | Bone Turnover Markers | PINP at 12months | 52.6422 ng/ml | Standard Deviation 20.56123 |
| 99Tc-MDP | Bone Turnover Markers | CTX before treatment | 0.4657 ng/ml | Standard Deviation 0.25277 |
| 99Tc-MDP | Bone Turnover Markers | CTX at 12months | 0.3707 ng/ml | Standard Deviation 0.21062 |
| Fosamax | Bone Turnover Markers | CTX at 12months | 0.1771 ng/ml | Standard Deviation 0.16019 |
| Fosamax | Bone Turnover Markers | PINP before treatment | 29.255 ng/ml | Standard Deviation 29.46603 |
| Fosamax | Bone Turnover Markers | CTX before treatment | 0.1526 ng/ml | Standard Deviation 0.14138 |
| Fosamax | Bone Turnover Markers | PINP at 12months | 20.56123 ng/ml | Standard Deviation 25.34437 |
Secondary
Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100)
The health related quality of life was measured by 36-item Short Form Health Status Survey questionnaire (SF-36). The minimum and maximum values were 0 and 100, respectively. Higher scores mean a better a better outcome. The questionnaire includes 36 items that can be classified into the following eight health status subscales: Physical Functioning, Physical Role Limitations, Bodily Pain, General Health Perception, Vitality, Social Functioning, Emotional Role Limitations, and Mental Health. A standardized Physical Component Summary and a standardized mental component score were calculated. The physical component summary and mental component summary represent the deviation from the reference population in Sweden. Higher scores mean a better a better outcome.
Time frame: baseline, 6 months, and 12 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 99Tc-MDP | Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | Physical component summary at baseline by 36-item Short Form Health Status Survey questionnaire | 61.4 scores on a scale |
| 99Tc-MDP | Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | Physical component summary at 6months by 36-item Short Form Health Status Survey questionnaire | 67.587 scores on a scale |
| 99Tc-MDP | Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | Physical component summary at 12months by 36-item Short Form Health Status Survey questionnaire | 69 scores on a scale |
| 99Tc-MDP | Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | Mental component score at baseline by 36-item Short Form Health Status Survey questionnaire | 65.7 scores on a scale |
| 99Tc-MDP | Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | Mental component score at 6months by 36-item Short Form Health Status Survey questionnaire | 69.0359 scores on a scale |
| 99Tc-MDP | Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | Mental component score at 12months by 36-item Short Form Health Status Survey questionnaire (0-100) | 69.2645 scores on a scale |
| Fosamax | Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | Mental component score at 6months by 36-item Short Form Health Status Survey questionnaire | 66.24 scores on a scale |
| Fosamax | Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | Physical component summary at baseline by 36-item Short Form Health Status Survey questionnaire | 64.4 scores on a scale |
| Fosamax | Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | Mental component score at baseline by 36-item Short Form Health Status Survey questionnaire | 65.7 scores on a scale |
| Fosamax | Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | Physical component summary at 6months by 36-item Short Form Health Status Survey questionnaire | 69.09 scores on a scale |
| Fosamax | Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | Mental component score at 12months by 36-item Short Form Health Status Survey questionnaire (0-100) | 67.087 scores on a scale |
| Fosamax | Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | Physical component summary at 12months by 36-item Short Form Health Status Survey questionnaire | 68 scores on a scale |
Secondary
Side Effects
A transient rash and phlebitis, gastrointestinal reaction.
Time frame: 6 months, and 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 99Tc-MDP | Side Effects | abdominal pain | 0 side effects |
| 99Tc-MDP | Side Effects | dyspepsia | 0 side effects |
| Fosamax | Side Effects | abdominal pain | 2 side effects |
| Fosamax | Side Effects | dyspepsia | 4 side effects |